A MAGAZINE FROM THE TUBEROUS SCLEROSIS ALLIANCE

Winter 2012 | VOLUME 126

Unlocking a Cure for Tuberous Sclerosis Complex A White Paper by Vicky Holets Whittemore, PhD page 6

TSC Clinics “Up Close” page 12

Promising Science on the Possibility of Preventing Epilepsy page 16

Message from the Leadership

801 Roeder Road, Suite 750 Silver Spring, MD 20910 USA (301) 562-9890 Toll-free: (800) 225-6872 Fax: (301) 562-9870 www.tsalliance.org

Kari Luther Rosbeck, President & CEO Henry Shapiro, Chair, TS Alliance Board of Directors

WINTER 2012 • Volume 126 Kari Luther Rosbeck

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President and Chief Executive Officer

s 2012 begins, the TS Alliance is poised for another successful year on so many fronts. We are thrilled to have just released Unlocking the Cure for Tuberous Sclerosis Complex: An Assessment of Scientific and Research Needs, a white paper written by Vicky Holets Whittemore, PhD. This publication is so important that we’re reprinting it in Perspective as this issue’s cover story. Our goal with this white paper was to identify key areas of TSC clinical care and research where significant progress has been made; areas where research is needed; the barriers to progress in TSC research; and the unmet clinical needs of people with TSC. Dr. Whittemore interviewed 27 key opinion leaders to assess these issues, and the resulting publication provides a road map of where we’ve been, but more important, where TSC research needs to go to ensure a better quality of life for anyone affected by TSC. We believe you will find the results compelling and encouraging. The new year also brings a new slate of Directors to the TS Alliance Board. We’d like to thank outgoing board members Will Cooper, Cathy Krinsky, Kathy Mayrsohn and David Schenkein, MD, who all worked tirelessly on your behalf. We also want to acknowledge David Parkes, the former board chair, for yeoman’s efforts leading the board and staff. He has inspired many of us to be the best we can be. We have four new board members to introduce. David Michaels brings more than 30 years of finance expertise to the board. Debora Moritz, whose son Griffin has TSC, has been active in her local Community Alliance and a key member of our government advocacy efforts. Robert Moss co-chairs the TS Alliance of Metro DC and co-founded seizuretracker.com; his son Evan has TSC. Finally, Rebecca Anhang Price, PhD, has a son with TSC named Elijah and offers vast experience in research and health-specific marketing and strategic planning. While the new white paper sets the stage for the next decade of research, the TS Alliance will sponsor a TSC Clinical Consensus Conference this coming June in Washington, DC. This conference will gather the top experts in TSC who will meet to define and update the latest in TSC diagnosis, surveillance and treatment options. Moreover, the TS Alliance will then present four Regional TSC Conferences later this year, where the Consensus Conference results will be presented. You’ll find more information about the regional conferences on page 22. Of course, we also have several major events scheduled, including the Step Forward to Cure TSC walkathons, Comedy for a Cure in Hollywood, and a new New York event called Art for a Cure. We are also pleased to announce the first “national” Step Forward to Cure TSC event to be held in Washington, DC on the National Mall. You’ll find details about all these events elsewhere in this issue. As you’ll read in the conclusion to this issue’s cover story, TSC research “is poised for providing new therapies that modify progression of the disease, and possibly even prevent some of the most devastating manifestations.” So please know: the TS Alliance staff, Board of Directors, and volunteers are committed to making sure everything possible is done to improve the lives of each of our constituents.

Jaye D. Isham

Senior Director, Marketing and Communications Managing Editor If you have opinions, questions or articles for Perspective, we would like to hear from you. Please contact the managing editor to obtain a submissions form and guidelines. Perspective is intended to provide basic information about tuberous sclerosis complex. It is not intended to, nor does it, constitute medical or other advice. The Tuberous Sclerosis Alliance (TS Alliance) does not promote or recommend any treatment, therapy, institution or health care plan. Readers are warned not to take any action without first consulting a physician. Commentary expressed herein reflects the personal opinions of the author and does not necessarily reflect the official views of the TS Alliance. Information contained in the TS Alliance database is confidential and not provided nor sold to third parties. Perspective is published quarterly by the National Tuberous Sclerosis Association, Inc. d/b/a Tuberous Sclerosis Alliance, a 501(c)(3), charitable organization. ©Copyright 2012 by the Tuberous Sclerosis Alliance. All Rights reserved. Materials may not be reproduced without written permission. Direct requests for reprint permission to the managing editor.

Board of Directors

Henry Shapiro, Chair Matt Bolger, Vice Chair Keith Hall, Secretary Celia Mastbaum, Treasurer David Parkes, Immediate Past Chair Julie Blum Mark Carroll Peter Crino, M.D., Ph.D. Rita DiDomenico Reiko Donato William Ford Jennifer Glassman Steven Goldstein Ron Heffron Elizabeth Henske, M.D. Linda Jackson Alan Marshall Ted Mastroianni David Michaels Debora Moritz Robert Moss John Nicholson, M.D., M.B.A. Courtney O’Malley Rebecca Anhang Price, Ph.D. Judith Shoulak Elizabeth Thiele, M.D., Ph.D.

Endowment Fund Board of Directors Mark Carroll, Chair MaryJane Mudd, Secretary Michael Augustine, Treasurer William Ford Robert W. Groves III Michael Rosen Thurston

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Special Events

submitting donations is the day of your walk by turning them in at the registration table. Qualified winners will then be entered into a national drawing selected by our President & CEO Kari Luther Rosbeck on December 1, 2012.  The winner will then be contacted and congratulated by Kari.

TS Alliance of Greater Alabama

2012 Schedule To register for a walk in your area go to www.StepForwardtoCureTSC.org. Check back often for updated dates and locations.

Step Forward to Cure TSC® Nationally Sponsored By:

Date: April 14, 2012 Location: Emmet O’Neal Library, Mountain Brook, AL Event Chair: Carole Pitard [email protected]

TS Alliance of Arizona Date: April 28, 2012 Location: Eldorado Park, Scottsdale, AZ Event Chair: Debora Moritz [email protected]

TS Alliance of Atlanta/ North Georgia Date: May 12 2012 Location: Gerrard Landing Park, Roswell, GA Event Chair: Reiko Donato [email protected]

National Honorary Chair, Julianne Moore

TS Alliance of the Carolinas Join our NEW Circle of Champions a nd

be entered into a national drawing to win a flat screen TV.  (Rules: Any individual raising $10,000 or more will be honored in Perspective in our Circle of Champions listing.  In addition, any individual who raises $10,000 or more through online donations, checks, cash or matching gifts qualifies for the national drawing to win a Big Screen Plasma HDTV.  The deadline for

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Date: October 2012 Location: Lake Murray Dam, Lexington, SC Event Chair: Dee Triemer [email protected]

Date: May 5, 2012 Location: Lake Storey Recreational Area, Galesburg, IL Event Chair: Karen JohnsonWenger, [email protected]

TS Alliance of Connecticut Date: June 9, 2012 Location: Rothberg Institute, Guilford, CT Event Chair: Jennifer Waldron [email protected]

TS Alliance of the Dallas/Ft. Worth Area Date: May 19, 2012 Location: Frisco Commons Park, Frisco, TX Event Chair(s): Scott & Mandy Striegel, stepforwarddfw@yahoo. com

TS Alliance of Delaware/Lehigh Valley Date: September 2012 Location: Gring’s Mill, Wyomissing, PA Event Chair: Shelly Richards [email protected]

TS Alliance of the Delta Region Date: May 5, 2012 Location: Jambalaya Park, Gonzales, LA Event Chair: Samantha Glass [email protected]

TS Alliance of Florida Date: October 2012 Location: TBD, North Carolina Event Chair: Amy Quintana [email protected]

Date: October 2012 Location: Tropical Park, Miami, FL Event Chair: Vanessa Vazquez [email protected]

TS Alliance of Greater Chicago

TS Alliance of Heartland

Date: June 2012 Location: TBD, Metro Chicago Area Event Chair: Dee Triemer [email protected]

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Date: September 8, 2012 Location: Raccoon River Park, West Des Moines, IA Event Chair: Cindy & Ryan Blackard, [email protected]

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Special Events TS Alliance of Houston

TS Alliance of the Rocky Mountain Region

Location: Auburndale Park, Auburndale, MA Event Chair(s): Stacie Verrill [email protected]

Date: May 5, 2012 Location: MacGregor Park, Houston, TX Event Chair: Bill & Taska Fields [email protected]

TS Alliance of New Jersey Date: October 2012 Location: TBD Event Chair: Dee Triemer [email protected]

TS Alliance of Indiana Date: June 2012 Location: Forest Park, Noblesville, IN Event Chair: Faye Robison [email protected]

TS Alliance of Southern California

TS Alliance of New York Date: September 22, 2012 Location: Onondaga Lake Park, Liverpool, NY Event Chair: Stephanie Langstaff [email protected]

TS Alliance of Intermountain West Date: September 8, 2012 Location: Liberty Park, Salt Lake City, UT Event Chair: Alisa Lambros [email protected]

Date: September 15, 2012 Location: Wantagh Park, Wantagh, NY Event Chairs: Denise & Rob Spear [email protected]

TS Alliance of Greater Kansas City

TS Alliance of Northern California

Date: September 15, 2012 Location: Shawnee Mission Park, Shawnee, KS Event Chair: Denise Breen [email protected]

Date: October 2012 Location: Heather Farm Park, Walnut Creek, CA Event Co-Chairs: Diane Burgis [email protected]

TS Alliance of Metro DC Join us for a new national walk that signifies standing together and being counted as a national presence! Date: June 16, 2012 Location: National Mall, Washington, DC Event Chair: Linda Gorsuch [email protected]

TS Alliance of Michigan Date: June 9, 2012 Location: Granger Meadows Park, Lansing, MI Event Chair: Treasa Bolger [email protected]

TS Alliance of New England

Date: May 19, 2012 Location: El Dorado Park – East, Long Beach, CA Event Chair: Tresha Bisang, Cindy Chernow, Barb O’Neil and Dawn Redfield. Dawn - [email protected]

TS Alliance of St. Louis & S. Illinois Date: September 22, 2012 Location: Cliff Cave Park, St. Louis, MO Event Chair: Gwen Montaigne & Donna Bullard [email protected] [email protected]

TS Alliance of the Upper Midwest

TS Alliance of Ohio Date: June 2012 Location: Pine Hills Lake Park, Mason, OH Event Co-Chairs: Lola & Carl Centeno [email protected] Date: October 2012 Location: Roman Park, Westlake, OH Event Chair: Michelle Blood [email protected]

Date: May 20, 2012 Location: Como Park, St. Paul, MN Event Chair: Maria Gibbons [email protected]

TS Alliance of Western Pennsylvania Date: September 2012 Location: Bradys Run Park, Beaver Falls, PA Event Chair: Mike Seman [email protected]

TS Alliance of Wisconsin

TS Alliance of the Pacific Northwest Region Date: June 2012 Location: TBD Seattle, WA Event Chair: Dee Triemer [email protected]

Date: September 2012

Date: May 19, 2012 Location: EB Rains Park, Northglenn, CO Event Chair: Dana Holinka [email protected]

Date: September 22, 2012 Location: Grant Park, S. Milwaukee, WI Event Chair: Kristin Champagne [email protected]

CONTINUED ON PAGE 21

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Government Relations Update Congress Approves $5.1 Million for TSC Research On December 17, 2011, the Senate cleared the final fiscal year 2012 Consolidated Appropriations Act, which funds a number of government agencies, including the Department of Defense (DoD). We are pleased to report that, during this difficult fiscal year, an appropriation of $5.1 million for the Tuberous Sclerosis Complex Research Program (TSCRP) was included in the final bill. This legislation was signed into law on December 23, 2011. As a result, the TSCRP has now received an aggregate appropriation

of $41 million from Congress since the program was first created in fiscal year 2002. This would not have been possible without the tireless efforts of our advocates. Despite the enormous pressure in Washington, D.C. to cut spending, our advocates marched on Washington last Spring and kept pressing their elected officials from home to ensure this important program survived in this difficult fiscal environment.

“March on Capitol Hill” Scheduled for February 22 Please join us February 22, 2012 in Washington, D.C. for the TS Alliance’s

annual “March on Capitol Hill.” This is an excellent opportunity to meet with members of Congress and their staff to advocate for continued funding in fiscal year 2013 for the TSCRP. For more information, contact Katie Smith at (800) 225-6872 or visit www.tsalliance.org/ActionTeam.aspx.

TSC Clinical Consensus Conference Planned

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h e T S A lli an c e i s s p o ns o ring a TSC Clinical Consensus Conference in June 2012 in Washington, DC. This conference will bring together international experts to update diagnostic criteria and to recommend best practices for diagnosis, surveillance, and management of TSC. The last such conference was held in 1998. Since that time, we have learned much about the genetics and cellular mechanisms of the disease. Also, the therapeutic options avail ab l e h ave c h ange d

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dramatically, including the approval of everolimus for inoperable SEGAs and vigabatrin for infantile spasms in just the last three years. Drs. Hope Northrup (University of Texas at Houston) and Darcy Krueger (Cincinnati Children’s Hospital Medical Center) are co-chairing this important conference. Together with the TS Alliance staff, they have recruited key international experts to lead working groups on each of the manifestations of TSC that can affect so many parts of the body and mind. These leaders

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are inviting specific clinicians from around the world to participate in working groups at the 2012 conference and to engage in pre-work leading up to the conference to ensure a comprehensive, productive, and focused discussion when they come together in Washington. The recommendations of the consensus conference will be published as soon as possible and distributed around the globe to help improve the consistency and quality of care to individuals with TSC everywhere.

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Unlocking a Cure for Tuberous Sclerosis Complex:

An Assessment of Scientific Progress and Research Needs A W h i te P ape r b y V i c k y H olets W h i ttemo r e , P h D

Abstract Significant progress has been made in tuberous sclerosis complex (TSC) research and clinical care following cloning of the TSC1 and TSC2 genes and identifying their role in the mammalian target of rapamycin (mTOR) signaling pathway. The goal of this study was to identify areas of highest research need in TSC. A survey of basic, translational and clinical research key opinion leaders (KOLs) was conducted to identify the significant progress that has been made, the areas of TSC research where less progress has been demonstrated, unmet medical needs of individuals with TSC, and future research and clinical needs, as well as barriers to progress. A telephone survey was conducted 27 KOLs, and the results were collated into a summary of the findings, which was reviewed by the KOLs. Comments and clarifications were incorporated into the final results. The results highlighted research that moved the understanding of the underlying mechanism(s) of TSC forward in a significant way and that resulted in improvement in the clinical care and quality of life for individuals with TSC. The results also highlighted areas where more research is needed. The most significant progress in TSC was identifying and characterizing the role of the TSC1 and TSC2 genes in the mTOR signaling pathway. Increased focus on research on the central nervous system manifestations of TSC and clinical care for adults with TSC is warranted.

Introduction Tuberous sclerosis complex (TSC) is a genetic disorder with an estimated incidence of one in 6,000 live births1. TSC is a multisystem disorder that may affect one or several organ systems, with variable penetrance even within the same family. Two genes, the TSC1 gene on chromosome 92 and the TSC2 gene on chromosome 16 3 have been identified. More than 2/3 of the cases are reported to be spontaneous mutations (de novo mutations), with only 1/3 of the cases being familial. The first detailed description of the central nervous system symptoms and pathology of TSC was provided by Bourneville, who used the term “tuberous sclerosis of the cerebral convolutions” to describe a child with seizures and learning disability4. Over the years, the diagnosis of TSC has 6

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undergone significant changes as more was learned about the disease, the genes were identified allowing for molecular diagnostic testing, and the variability of the manifestations of the disease was appreciated5,6. Initially, the diagnosis was based on the Vogt triad of mental retardation, facial angiofibromas (incorrectly called adenoma sebaceum), and seizures7. Manuel Gomez, MD was the first to recognize and document the full extent of the manifestations of disease and established the first diagnostic criteria that based the diagnosis on identifying the presence of major and minor manifestations that together would lead to a definite, probable or possible diagnosis8. These diagnostic criteria were later revised to reflect new knowledge about the disease 9, and continue to be used for clinical diagnosis of TSC in conjunction with molecular diagnostic testing. While

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many individuals with TSC will develop a severe neurological phenotype (epilepsy, autism spectrum disorder, cognitive disability), it is now clear that individuals with TSC may have very minor clinical features and only present for diagnosis in adulthood due to medical issues and/or after one of their children is diagnosed with TSC. There are no recent epidemiological studies in the USA that document the true incidence and prevalence of TSC, and the previous studies were completed more than 20 years ago on a small population of individuals with TSC10. The majority of individuals with TSC will have a normal life expectancy. However, medically refractory epilepsy, polycystic kidney disease, renal angiomyolipoma with life-threatening hemorrhage, renal cell carcinoma, cardiac failure due to cardiac rhabdomyomas, and progressive lymphangioleiomyomatosis

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(LAM) may impact a n i n d i v i d u a l ’s l i fe expectancy10. In addition, the presence of learning disabilities, psychiatric diagnoses, including anxiety disorders, depression, and autism spectrum disorder, may severely impact an individual’s quality of life11,12,13 . TSC can affect almost every organ system with significant variability between individuals with TSC. There is a high incidence of many significant clinical problems in individuals with TSC overall, including epilepsy, autism spectrum disorder, anxiety disorder, benign tumor grow th and L AM 14 . Progress in understanding the underlying mechanisms of disease has been greatly assisted by the identification of the TSC1 and TSC2 genes and the ability to perform molecular diagnostic testing. The role of the TSC1/2 gene complex in the mammalian target of rapamycin (mTOR) signaling pathway led to the development of numerous animal models of TSC that are now utilized in research studies. Having gone from gene cloning to understanding the role of the genes to clinical trials in a short period of time has placed TSC in the role of a “model system” for studying and better understanding a rare genetic disorder14,15. Understanding the factors that lead to tumor growth, epilepsy or autism spectrum disorder in individuals with TSC may lead to a better understanding of the underlying mechanism(s) in these disorders in the general population15. The goal of this survey is to identify the areas of TSC clinical care and research where significant progress has been made, areas where research is needed, the barriers to progress in TSC research, and the unmet clinical needs of individuals with TSC. This survey attempts to identify the key challenges in finding new treatments and a cure for TSC, as well as to discuss issues discussed by key opinion leaders in the TSC community regarding the needs of the research and clinical community in their research efforts

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and to provide care for individuals with TSC. Recommendations are provided for the critical research areas that need focused attention, support and funding in order to find a cure for TSC while improving the lives of those affected. Identifying these areas will be the first step toward unlocking a cure for TSC, and hopefully for many other disorders.

Methods Twenty seven key opinion leaders (KOLs) were interviewed regarding their views and opinions on the progress in our understanding of the clinical features of TSC, the status of basic and translational science on TSC, areas of unmet needs in both clinical care and research, and barriers and challenges to making progress in these areas. The KOLs are all experts in basic, translational and/or clinical research on TSC, as well as health care providers who have a particular interest and expertise in providing clinical care for individuals with TSC. The KOLs were interviewed by telephone by the author, and all were asked the same questions for the survey during the interview. The questions focused on 1) the major advances in TSC research; 2) the barriers to progress in TSC research and clinical care; and 3) the unmet clinical needs of individuals with TSC. A draft of the survey results were reviewed by all of the KOLs and additional comments and clarifications were incorporated into the final discussion and recommendations.

Defining a “Cure” for TSC The consensus of the KOLs is that finding a “cure” for TSC will be a significant challenge due to the genetic nature of the disease and the fact that so many of the individuals with TSC have de novo mutations. Gene therapy is not likely to be a meaningful approach to treating TSC because the most significant manifestations of the

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disease, those affecting the central nervous system, are in place at birth. However, improvements in diagnosis of TSC leading to earlier diagnosis and recognition of those individuals who are at risk for epilepsy, neurodevelopmental and cognitive delays would lead to earlier treatment and therapies that may prevent the impact of the disease. Currently, the goal would be to identify treatments that normalize the lives of individuals with TSC so that they can lead healthy and productive lives.

Areas of TSC Research with Significant Progress There was very little research on TSC until the TSC1 and TSC2 genes were identified in the 1990s, and the subsequent findings that the protein products of these genes, hamartin and tuberin, respectively, play a critical role in regulating cell growth, cell proliferation and organ size16-18 and in the mTOR signaling pathway19,20,. The cellular effects of TSC1/2 gene disruption identified in vitro were also shown in some tumors from TSC rodent models and human TSC or LAM lesions19,22-31. These findings, along with preclinical studies that showed a response to treatment with mTOR inhibitors19,22,33 led to the current clinical trials. Most notably, recent studies have shown that treatment of animal models of TSC with mTOR inhibitors can not only prevent the onset of seizures34 and cognitive deficits 35 in young animals, but can also treat seizures34 and reverse cognitive deficits 35 in older animals. These significant findings indicate that deficits and manifestations of disease due to the underlying molecular mechanism in TSC may be both preventable and in some cases, reversible 36,37 . At this time, clinical trials for renal angiomyolipomas (AMLs) 38,39 , subependymal giant cell astrocytomas (SEGAs) 40,41, facial angiofibromas, lymphangioleiomyomatosis (sporadic

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and associated with TSC)39,42, cognition and epilepsy are either completed or currently underway. Based on the data from a Phase II trial 41, the Food and Drug Administration approved Afinitor®, manufactured by Novartis Oncology, for treatment of SEGAs associated with TSC. Completion of the Phase III trial is expected in 2011, as well as completion of the Phase III trial for renal angiomyolipomas. The results of the completed trials indicate that SEGAs and renal AMLs decrease in size in response to treatment with mTOR inhibitors, but that the majority of tumors regrow once the treatment is stopped38,40. The rapid progress from identification of the genes, to identification of their role in the mTOR pathway, to clinical trials has provided specific treatments for individuals with TSC for the first time. Although the clinical trials with mTOR inhibitors show reduction in the size of tumors in individuals with TSC, results of the clinical trials show that the tumors regrow once the treatment is stopped. The KOLs agreed that there is significant need to identify new drug targets and potential treatments for TSC that not only reduce the size of the tumors, but cause the tumors to permanently regress. The need for biomarker(s) that can be utilized to study progression of disease as well as response to treatment are needed for TSC and LAM. A recent study shows that blood levels of VEGF-D may be a reliable biomarker for individuals with LAM43, but it remains to be characterized in a large group of individuals with TSC.

Recommendations: • Expand preclinical and clinical research to identify new drug targets (such as mTORC1, mTORC2, Rheb, VEGF-D, MAPK, LKB1/ AMPK pathway, among others) and potential new compounds and drugs to treat the various manifestations of TSC by testing drugs in combination with, or instead of mTOR inhibitors. 8

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• Identify and characterize biomarkers that measure progress of disease and/or response to treatment in both TSC and LAM. • Continue research to understand the role of gene dysfunction that leads to specific manifestations of TSC, specifically cognitive deficits and epilepsy, such that prevention strategies can be identified.

Areas in Need of Additional Research Although much is now known about the role of the TSC1/2 complex in the mTOR signaling pathway, very little is understood about how disruption of this complex due to a mutation in one of the TSC genes actually results in the specific manifestations in TSC or the timing of their appearance in individuals with TSC. There is also very little known about the significant variability of the disease, even between family members who carry the same mutation in either the TSC1 or TSC2 gene. In addition, there is a significant number of individuals whose mutation can not be identified using modern sequencing techniques for which the suggestion has been made that there may, in fact, be additional genes for TSC that have not been identified. Clearly the most debilitating manifestations of TSC are those that affect the central nervous system. Attempts have been made to correlate the number, location and size of cortical tubers with intellectual impairment and autism spectrum disorder. However, there are individuals with TSC who have a significant tuber load and have normal intelligence while there are others with very little tuber load who have significant intellectual disability and/or autism spectrum disorder. Early onset of seizures that are not well controlled with medication appears to be one of the most significant factors involved in cognitive outcomes, but no large

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scale studies have documented this correlation.

Recommendations: • Identify the underlying mechanism(s) involved in the development of specific manifestations of TSC. • Focus genetic studies on identification of additional genes for TSC (i.e., TSC3, TSC4, etc.) and/ or mutations that are not currently detected using sequencing or other current techniques. • Expand research on the potential for genetic modifiers that lead to variability of phenotype between individuals with the same mutation so that there is a clearer path to predict severity of outcome and lead to personalized medical care for each individual with TSC. • Gain an understanding of the underlying molecular mechanism(s) that result in epilepsy, autism spectrum disorder, learning disabilities, anxiety and other psychiatric conditions in individuals with TSC, and develop treatments and preventative strategies where possible. • Increase basic research on the causes(s) of cognitive and intellectual disabilities using animal models of TSC and perform critical clinical studies of individuals with TSC.

Unmet Medical Needs of Individuals with TSC There is a significant need for early diagnosis and aggressive treatment of TSC in order to optimize outcomes for individuals with the disease. Too many individuals with TSC, especially infants and young children, go for weeks with undiagnosed seizures that if diagnosed early and treated aggressively would likely lead to better outcomes for these children. There was a consensus of the KOLs that new screening tools are

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needed to diagnose infants with TSC prior to the onset of seizures, whenever possible, and to intervene with effective treatments as quickly as possible when seizures begin. Some KOLs suggested that it may be possible to prevent seizures in infants with TSC by early screening of the EEG and treatment of an abnormal EEG prior to the onset of seizures. Since as many as 40% of infants with TSC develop infantile spasms, identifying methods for early diagnosis and preventative treatment would result in optimal outcomes for these children. The KOLs noted that there has been research done that identifies the cognitive and intellectual disabilities in individuals with TSC, but very little research has addressed the potential cause(s) and/or treatments. The first clinical trial to directly address a treatment for the neurocognitive issues in children with TSC began in 2011, but clearly much more basic research utilizing animal models of TSC is needed to gain an understanding of the causes of the cognitive and intellectual disabilities in TSC. The KOLs also agreed that there is a critical need for physicians who treat adults with TSC to have a better understanding of the possible manifestations of the disease and to treat the whole individual in a comprehensive and multidisciplinary manner. A network of TSC Clinics in the USA provides clinical care to individuals with TSC, with 18 out of the 30 clinics providing care to adults with TSC. However, for many individuals with TSC the transition from pediatric to adult care is not smooth, as for many individuals with rare genetic disorders, and in some areas this care is nonexistent.

Recommendations:

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Barriers to Progress in TSC Research For many years, the barriers to progress in TSC research were the lack of researchers, clinicians and funding for this rare genetic disease. A small, but very dedicated group of researchers pushed the knowledge about TSC from the identification of the genes, to an understanding of the role of the TSC1/2 complex in the mTOR pathway, to the current clinical trials in less than 15 years. In the grand scheme of disease research, this is rapid and remarkable progress. In the lives of individuals with TSC, and for those who have lost their lives to the disease, the progress is not rapid enough. The TS Alliance provided the first research grant award in 1984, and

since that time has funded $15.3 million in basic, translational and clinical research. The goal of the TS Alliance has been to fund small seed grants that allowed investigators to develop preliminary data in order to compete for funding from larger organizations and the National Institutes of Health. The TS Alliance has also provided funding for resource development that would assist the TSC community overall – annual workshops to bring together the genetic researchers at the American Society of Human Genetics meeting for exchange of information and data; international TSC research conferences in 1998, 2002, 2006 2007, 2009 and 2011; support for the TSC1/2 Variation Database; development and expansion of the TSC Natural History Database that contains clinical data on more than 1,100 individuals with TSC; and animal models of TSC. Support for TSC research funded by NIH has increased significantly since the identification of the genes and the role of the proteins in regulating the mTOR in 2002 (see Figure 1). A tremendous boost for TSC research funding has come from the TSC Research Program in the Congressionally Directed Medical Research Program in the Department of Defense. Through 2011, $35.9 million have been provided through this program specifically for TSC research (Figure 1).

FIGURE 1

TSC Research Grant Funding 40,000,000 35,000,000 30,000,000 25,000,000 Dollars

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National Institutes of Health

15,000,000

TSCRP, CDMRP, DoD Tuberous Sclerosis Alliance

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• Develop screening methods that provide early diagnosis of TSC. • Identify infants with TSC who are at risk for developing seizures, especially infantile spasms, and develop preventative treatments

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leading to optimal clinical outcomes. • Continue to increase the knowledge of the impact of TSC on adults with the disease and increase the number of centers that provide comprehensive, multidisciplinary care for these individuals. • Identify and characterize biomarkers for detecting disease progression and response to treatment.

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FY03 FY04 FY05 FY06 FY07 FY08 FY09 FY10 FY11 Fiscal Year

Please note: TS Alliance funding for FY10 includes 18 months due to a change in fiscal year.

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However, even with all of these avenues for research funding, funding is incredibly competitive at all levels. The KOLs stated the need for additional research funding at all levels in order to expand current research efforts. Many of the KOLs also noted the significant need for a clinical trial network that would help to facilitate, streamline and support the development and performance of clinical trials. There was also substantial support for increased funding specifically focused on the neurological manifestations of TSC which often have the largest impact on the quality of life for individuals with TSC and their families.

Recommendations: • Increase funding for TSC research at all levels. • Increase support for translational research, including preclinical drug screening and testing of compounds and drugs for use to treat manifestations of TSC. • Provide support for a clinical trial network that would increase the number of clinical trials for TSC, as well as increase efficiency and reduce cost to carry out the trials. • Continue to support and expand TSC research resources that are utilized by the community (TSC Natural History Database, TSC1/2 Variation Database, sharing of animal models, cell lines, etc.).

Conclusions In conclusion, research on TSC is poised for providing new therapies that modify the progression of the disease, and possibly even prevent some of the most devastating manifestations. It will likely not be possible to unlock a cure for TSC in the near future, but with focused research efforts new treatments will significantly improve the lives of those affected, and will provide clues for treatment of other disorders.

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Key Opinion Leaders Interviewed for White Paper E. Martina Bebin, MD, MPH; University of Alabama, Birmingham, AL John Bissler, MD; Children’s Hospital Medical Center, Cincinnati, OH John Blenis, PhD; Harvard University, Boston, MA Peter Crino, MD, PhD; University of Pennsylvania, Philadelphia, PA Paolo Curatolo, MD; Tor Vergata University Hospital, Rome, Italy Sandra Dabora, MD, PhD; Brigham & Women’s Hospital, Boston, MA Orrin Devinsky, MD; New York University, New York, NY Petrus de Vries, MD, PhD; Cambridge University, Cambridge, UK Kevin Ess, MD, PhD; Vanderbilt University, Nashville, TN Jane Fountain, PhD; National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD David Franz, MD; Children’s Hospital Medical Center, Cincinnati, OH Michael Frost, MD; Minnesota Epilepsy Group, St. Paul, MN Kuan-Li Guan, PhD; University of California, San Diego, CA Elizabeth Petri Henske, MD; Brigham & Women’s Hospital, Boston, MA Sergiusz Jozwiak, MD, PhD; The Children’s Memorial Health Institute,, Warsaw, Poland David Kwiatkowski, MD, PhD; Brigham & Women’s Hospital, Boston, MA Brendan Manning, PhD; Harvard University School of Public Health, Boston, MA Hope Northrup, MD; University of Texas Health Science Center, Houston, TX Mustafa Sahin, MD, PhD; Children’s Hospital/Harvard University, Boston, MA Julian Sampson, MB; Cardiff University, Cardiff, UK Alcino Silva, PhD; University of California, Los Angeles, CA Elizabeth Thiele, MD, PhD; Massachusetts General Hospital, Boston, MA Cheryl Walker, PhD; University of Texas MD Anderson, Smithville, TX Howard Weiner, MD; New York University, New York, NY Michael Wong, MD, PhD; Washington University, St. Louis, MO Joyce Wu, MD; University of California, Los Angeles, CA Raymond Yeung, MD; University of Washington, Seattle, WA

References Osborne JP, Fryer A, Webb D. Epidemiology of tuberous sclerosis. Ann NY Acad Sci. 1991; 615:125-127. Van Slegtenhorst M, de Hoogt R, Hermans C, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997; 277(5327):805-808. The European Chromosome 16 Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell. 1993; 75(7):1305-1315. Bourneville DM. Sclérose tubérereuse des circonvultions cérébrales: idiotie et épilepsie hémiplégique. Arch Neurol (Paris). 1880; 1:81-91. Roach ES, Sparagana SP. Diagnostic criteria for tuberous sclerosis complex. D Kwiatkowski, E Thiele, V Whittemore, eds. Tuberous Sclerosis Complex. Weinheim, Germany: Wiley-VCH; 2010:21-25. Whittemore VH. The history of tuberous sclerosis complex. D Kwiatkowski, E Thiele, V Whittemore, eds. Tuberous Sclerosis Complex. Weinheim, Germany: Wiley-VCH; 2010:3-9. Vogt H. Zue Pathologie und pathologishcen Anatomie der verschiedenen Idiotieform. Monatsschr Psychiatr Neurol. 1908; 24:106-150. Gomez MR. Criteria for diagnosis. MR Gomez, ed. Tuberous Sclerosis. 2nd ed. New York, NY: Raven Press; 1988:

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Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol. 1998; 13(12):624-628. Shepherd CW, Gomez MR, Lie JT, Crowson CS. Causes of death in patients with tuberous sclerosis. Mayo Clin Proc. 1991; 66(8):792-796. de Vries PJ. Neurodevelopmental, psychiatric, and cognitive aspects of tuberous sclerosis complex. D Kwiatkowski, E Thiele, V Whittemore, eds. Tuberous Sclerosis Complex. Weinheim, Germany: Wiley-VCH, 2010:229-267. Webb DW, Fryer AE, Osborne JP. Morbidity associated with tuberous sclerosis: a population study. Dev Med Child Neurol. 1996; 38(2):146-155. Staley BA, Vail EA, Thiele EA. Tuberous sclerosis complex: diagnostic challenges, presenting symptoms, and commonly missed signs. Pediatrics. 2011; 127(1):e117-25; Epub 2010 Dec 20. Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med. 2006; 355(13):1345-1356. Thiele EA, Jozwiak S. Natural history of tuberous sclerosis complex and overview of manifestations. D Kwiatkowski, E Thiele, V Whittemore, eds. Tuberous Sclerosis Complex, Weinheim, Germany: Wiley-VCH, 2010:11-20. Gao X, Pan D. TSC1 and TSC2 tumor suppressors antagonize insulin signaling in in cell growth. Genes Dev. 2001; 15(11):1383-1392. Potter CJ, Huang H, Xu T. Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell. 2001; 105(3):357-368. Tapon N, Ito N, Dickson BJ, Hariharan IK. The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell. 2001; 105(3):345-355. Kenerson HL, Aicher LD, True LD, Yeung RS. Activated mammalian target of rapamycin pathway in the pathogenesis of tuberous sclerosis complex renal tumors. Cancer Res. 2002; 62(20):5645-5650. Manning BD, Tee AR, Logsdon MN, Blenis J, Cantley LC. Identification of the tuberous sclerosis complex2-tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol Cell. 2002; 10(1):151-162. Tee AR, Fingar DC, Manning BD, Kwiatkowski DJ, Cantley LC, Blenis J. Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci USA. 2002; 99(21):13571-13576. Gonchorova EA, Goncharov DA, Eszterhas A, et al. Tuberin regulates p70 S6 kinase activation and ribosomal protein S6 phosphorylation: a role for the TSC2 tumor suppressor gene in pulmonary lymphangioleiomyomatosis (LAM). J Biol Chem. 2002; 277(34):30958-30967. Kwiatkowski DJ, Zhang H, Bandura JL, et al. A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in TSC1 null cells. Hum Mol Genet. 2002; 11(5):525-534. El-Hashemite N, Walker V, Zhang H, Kwiatkowski DJ. Loss of Tsc1 or Tsc2 induces vascular endothelial growth factor production through mammalian target of rapamycin. Cancer Res. 2003; 63(17):5173-5177. El-Hashemite N, Zhang H, Henske EP, Kwiatkowski DJ. Mutation in TSC2 and activation of mammalian target of rapamycin signaling pathway in renal angiomyolipoma. Lancet. 2003; 361(9366):1348-1349. Crino PB. Molecular pathogenesis of tuber formation in tuberous sclerosis complex. J Child Neurol. 2004; 19(9):716-725. Manning BD, Logsdon MN, Lipovsky AI, Abbott D, Kwiatkowski DJ, Cantley LC. Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2. Genes Dev. 2005; 19(15):1773-1778. Marcotte L, Crino PB. The neurobiology of the tuberous sclerosis complex. Neuromolecular Med. 2006; 8(4):531-546.

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Zhang HH, Lipovsky AI, Dibble CC, Sahin M, Manning BD. S6K1 regulates GSK3 under conditions of mTORdependent feedback inhibition of Akt. Mol Cell. 2006; 24(2):185-197. Kenerson H, Folpe AL, Takayama TK, Yeung RS. Activation of the mTOR pathway in sporadic angiomyolipomas and other perivascular epitheliod cell neoplasms. Hum Pathol. 2007; 38(9):1361-1371. Ozcan U, Ozcan L, Yilmaz E, et al. Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Mol Cell. 2008; 29(5):541-551. Lee L, Sudentas P, Donohue B, et al. Efficacy of a rapamycin analog (CCI-779) and IFN-gamma in tuberous sclerosis mouse models. Genes Chromosomes Cancer. 2005; 42(3):213-227. Meikle L, Pollizzi K, Egnor A, et al. Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J Neurosci. 2008; 28(21):5422–5432.

Zeng L-H, Xu L, Gutmann DH, Wong M. Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex. Ann Neurol. 2008; 63(4):444–453. Ehninger D, Han S, Shilyansky C, et al. Reversal of learn+/ing deficits in a Tsc2 mouse model of tuberous sclerosis. Nat Med. 2008; 14(8):843–848. Tsai P, Sahin M. Mechanisms of neurocognitive dysfunction and therapeutic considerations in tuberous sclerosis complex. Curr Opin Neurol. 2011; 24(2):106-113. Napolioni V, Moavero R, Curatolo P. Recent advances in neurobiology of Tuberous Sclerosis Complex. Brain Dev. 2009; 31:104-113. Bissler JJ, McCormack FX, Young LR, et al. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med. 2008; 358(2):140-151. Davies DM, Johnson SR, Tattersfield AE, et al. Sirolimus therapy in tuberous sclerosis or sporadic lymphangioleiomyomatosis. N Engl J Med. 2008; 358(2):200-203.

Franz DN, Leonard J, Tudor C, et al. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol. 2006; 59(3):490-498. Krueger DA, Care MM, Holland K, et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010; 363(19):1801-1811. McCormack FX, Inoue Y, Moss J, et al. Efficacy and Safety of Sirolimus in Lymphangioleiomyomatosis. New Engl J Med. 2011; Mar 12, [Epub]. Young LR, Vandyke R, Gulleman PM, et al. Serum vascular endothelial growth factor-D prospectively distinguishes lymphangioleiomyomatosis from other diseases. Chest. 2010; 138(3):674-681.

Acknowledgements The author acknowledges the support of the Tuberous Sclerosis Alliance, and the expert review and discussions with Peter Crino, MD, PhD, Elizabeth Petri Henske, MD, Jo Anne Nakagawa, Kari Luther Rosbeck, Catherine Smith and Elizabeth Thiele, MD, PhD in completing this survey.

American Epilepsy Society (AES) Annual Meeting Overview

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he 2011 AES annual meeting held December 2-6 in Baltimore w a s—n o t s u r p r i s i n g l y—a n important scientific and networking event for the TSC community, given the impact that seizures have on so many individuals with TSC. In addition to five TS Alliance staf f members, the TSC community was represented by several TSC Clinic Directors, TS Alliance Professional Advisor y Board and International Scientific Advisory Board members, other academic and industry partners, and some current and former Board of Directors members. Drs. Elizabeth Thiele and Martina Bebin co-chaired the TSC Special Interest Group scientific session. This year’s topic was on the rationale and possible approaches for preventing the development of epilepsy in infants diagnosed with TSC prior to the onset of seizures. Drs. Sergiusz Jozwiak and Michael Wong gave presentations that they have summarized elsewhere in this issue of Perspective. The TS Alliance hosted a reception for approximately 50 AES attendees. Kari Rosbeck gave an update on the

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TS Alliance and the Unlock the Cure Campaign, Steve Roberds facilitated presentations and gave an update on the Drug Screening Program and the Natural History Database, Dr. Elizabeth Thiele presented on her TS Alliance funded research in partnership with Dr. Ray Yeung on Glucose Restriction, Karen Agricola and Dr. Anna Pinto presented on the Neurocognitive Clinical Trial, and Dr. Martina Bebin gave an overview of the planned Clinical Research Network. The TS Alliance hosted 10 families and nine TSC Clinic Directors for an informal Q&A and engaged in meaningful dialogue about next steps in research. TSC Clinic Directors in attendance were Drs. James Wheless, Martina Bebin, Elizabeth Thiele, Peter Crino, Tanjala Gipson (at Kennedy Krieger, Johns Hopkins and applying for TSC Clinic status), Michael Kohrman, Ajay Gupta, Susan Koh, Jim Riviello. We greatly appreciate the time that these individuals took away from a very busy AES meeting to engage with members of our community. TS Alliance Board of Directors member Julie Blum, former Board member and Corporate Advisory Board member

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John Richards with his wife Jordan, and incoming Board members Rebecca Anhang Price and Rob Moss with his wife Lisa attended, as well. The TS Alliance participated in Vision 20/20, a group consisting of advocacy organizations, AES leadership, neurology associations and government representatives from NINDS with the purpose of working together to find common messaging in epilepsy and to move more aggressively to better care and treatment of patients. One of the biggest initiatives for this group is the Institute of Medicine Report that will be completed at the beginning of 2012. The TS Alliance was a co-sponsor of this report and will receive an advance copy before general release. TS Alliance staff members also interacted with partners from NIH on the topic of epilepsy benchmarks, which track progress of the epilepsy field toward finding a cure for epilepsy. The next evaluation and update of the benchmarks will be in March 2013. Also, Steve and/or Kari engaged industry representatives from Athena, Cyberonics, Lundbeck, Novartis, Questcor, UCB, Upsher-Smith, and Visualase.

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TSC Clinics “Up Close”

Carol and James Herscot Center for Children and Adults with Tuberous Sclerosis Complex at Massachusetts General Hospital

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n 20 0 5, t hr e e ye ar s af te r D r. Elizabeth Thiele opened a TSC Clinic at Massachusetts General Hospital, a new state-of-the-art clinical and research facility named the Carol and James Herscot Center for Children and Adults with Tuberous Sclerosis Complex was established through the generosit y of the Herscots, who have a son with TSC. This article continues an interview series about the healthcare professionals who provide care and educational support to those affected by TSC. Meet Dr. Thiele and members of her team at the Herscot Center for TSC:

Dr. Thiele, what got you interested in TSC and was it what motivated you to open your TSC Clinic in 2002?

Elizabeth A. Thiele, MD, PhD,

Dr. Thiele, a collaboration between the Herscot Center for TSC and the WGBH Educational Foundation produced a comprehensive multimedia website called Living with TSC (w w w2.massgeneral.org/ livingwithtsc), which serves as a valuable information. What impact have the internet and the exchange of information through online community discussion groups made to providing care for your TSC patients and their families?

Professor of Neurology, Harvard Medical School Director, Herscot Center for Children and Adults with TSC Director, Pediatric Epilepsy Program at Massachusetts General Hospital

Margaux E. Black, BA , Research Assistant

Leigh Horne-Mebel, MSW, LICSW, BCD,

A: I guess I was initially interested in TSC due to the epilepsy, particularly the infantile spasms—and then became obsessed and pretty much totally committed because of the people and families I met living with TSC. The partnership and support of Carol and Jim Herscot have been invaluable in the establishment of the Herscot Center for TSC. We would not have been able to build the program we have today without them.

Clinical Social Worker A: I think the internet and online community discussion have had a huge impact on individuals living with TSC and their families. Information about TSC, and about organizations like the TS Alliance, are now “at people’s fingertips.” Just as important, people living with TSC are connecting in new ways; many families I follow around the country have developed supportive relationships and friendships. Tracking our website taught me a lot—within the

Anna M. Larson, BA, Research Assistant

Zaida Ortega, BS, Administrative Coordinator

Jan Paolini, MSN, RN, Nurse Coordinator

Heidi H. Pfeifer, RD, LDN, Clinical Nutrition Specialist 12

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first two years, it had over 200,000 visits from around the world. Information is powerful. Dr. Thiele, you are serving your second term on the TS Alliance Board of Directors. How has your professional experience helped you guide the organization closer to finding a cure for TSC and improving the lives of those affected? A: I love serving on the board. Although I do not have a family member living with TSC, I know many families that do, as well as have a pretty good knowledge of the clinical aspects of TSC and the science. Given that, I think I bring a slightly different perspective and balance to the board. I think I can help represent the clinical and scientific issues while at the same time serving as an advocate for many people and families living with TSC. Dr. Thiele, how has the organization changed since your first term on the board? A: I guess every organization changes over time—the people, the issues, the focus. What has impressed me most about the TS Alliance is the amount of passion and commitment by the staff, the board and the constituency, which have been steadfast. And while I have been on the board: WOW with regard to what is happening in the world of TSC. Dr. Thiele, you co-wrote two of 19 chapters and co - edited the TSC book, Tuberous Sclerosis Complex: Genes, Clinical Features,

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and Therapeutics (3rd Edition published in 2010). Are the challenges similar in getting a medical textbook or a research paper published when there are multiple contributors? If yes, what’s the #1 challenge? A: Working on the book was wicked fun, and a new and different experience. It was great fun, and cool that everyone involved was very excited about the book, meant to provide

A: Dietary therapy can be amazing effective in treating seizures in TSC and should definitely be given as an option in any person—baby, child or adult—with TSC and epilepsy. There are no strict criteria. The main limitation is usually the individual’s ability to tolerate the restrictions in diet. And implementing the diet can be difficult for the family, but as a TSC mother recent said, “there is nothing as difficult as watching your child have seizures.” I believe it should be considered when

fries, pizza, etc) we usually consider the diet as second or third line options. We have used dietary therapy in a few people (children and adults) who (or whose families) strongly preferred a dietary option over medications. Dr. Thiele, what’s new in the clinical research program at the Herscot Center for TSC? A: We are very lucky that there is an ever-continuing growth in interest and

Back row: Melanie Jennesson, MD Heidi Pfeifer, RD, LDN Margaux Black Susana Camposano, MD Agnies Van Eeghen, MD, PhD Anna Larson

Front row: Jan Paolini, MSN, RN Margaret Pulsifer, PhD Elizabeth A. Thiele, MD, PhD Zaida Ortega

comprehensive information about TSC to medical specialists, scientists, and families living with TSC. The #1 challenge was having the various authors meet the deadlines! I have a new and deep respect for editors! Dr. Thiele, you are an expert in using dietary therapies for treating intractable epilepsy. What are some of the criteria you follow in recommending the ketogenic or low glycemic diets to treat a TSC patient with seizures?

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seizures (either infantile spasms or other seizures) are not effectively (i.e. completely) controlled by medications. Dr. Thiele, are dietary therapies usually considered second or third options in TSC patients with seizures, or are they ever recommended as a first option instead of drug therapies in an individual with new onset seizures? A: Due to the difficulties of diet restrictions (i.e. no birthday cake, French

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passion about TSC at MGH, and we now have active clinical research programs involving almost every organ manifestation. Our main focus continues to be the neurologic involvement, particularly epilepsy, autism and the mental health aspects, but we also have active projects in kidney and liver involvement as well as heart, liver, pancreas and bone. Dr. Thiele, how do you manage to balance your time between seeing patients, teaching, speaking at research conferences, serving on

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advisory boards, doing interviews, conducting your research, and spending time with your family?

correlations for cognition, as well as nonneurologic manifestations of the disease, particularly liver angiomyolipomas..

as part of their educational program, but due to budgetary issues of most schools, those needs can’t be met.

A: Good question. I am still trying to find that balance. My family will always be first, and luckily they “get” me. They also “know” TSC pretty well, and my husband and kids have been to several conferences with me; I think for the first few years of his life my son thought everyone had TSC!

Zaida: To be a part of the outstanding team that we have working towards finding cures and helping our families in needs.

Is there time for relaxation; what do you do to unwind?

Dr. Thiele: To be able to provide ideal comprehensive care to individuals with TSC and their families is not at all easy, for several reasons, probably most importantly the multisystem involvement. It is not a type of care that is reimbursed by insurance companies, but is a type of care that is ideal, and is also deserved. So the challenge is how to make it happen. Carol and Jim Herscot have had a huge impact on the lives of many individuals and families that we follow. My main challenge is finding ways to sustain this level of care.

Margaux: The most challenging research days are those when I need to work at a computer (compiling and analyzing research data) rather than in clinic with patients and families. However, while working at the computer, I will think back to my experiences in clinic, remember the faces and stories of those I have met who are affected by TSC, and use these memories to keep me focused and motivated while I complete my tasks.

A: I have a very strong longstanding dream to learn to play the guitar. I have the guitar, I have the CD instruction (both gifts from my family over the past few years)—and one of my resolutions this year is to make it happen.

Questions for the Team What are your interests as they relate to TSC? Anna: I have a sustained interest in pediatric neurology and a deep passion for the clinical research in TSC that brings new hope for improved clinical care of individuals with this disease and their families. My current research in TSC includes an investigation of pancreatic neuroendocrine tumors and other related malignancies. Additionally, I am interested in the use of dietary therapy for the treatment of epilepsy in TSC. Heidi: Use of dietary therapy for treatment of seizures in TSC. Jan: Understanding the mental health and cognitive issues in the context of TSC. Leigh: The impact of this chronic disease on the patient and their family. Margaux: Dietary therapy for the treatment of epilepsy, genotype-phenotype 14

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What are the most challenging aspects of your work as it relates to the TSC Clinic?

Anna: It is hard to be patient. For translational investigators working closely with patients, there is real urgency to the scientific questions of mechanism and pathophysiology of disease, the natural history and epidemiology of TSC, and new therapeutic options. In-depth understanding and effective therapeutics take time. Yet layer by layer, investigators are learning more about TSC and how to best bring real and lasting improvement to the lives of all TSC patients. Heidi: Not being able to treat everyone with positive results. Jan: Coordinating the nursing care of patients with the parents, the school nurse, and the other multiple providers for the patient in their community. Leigh: Reduced financial resources in public schools and communities. It’s very difficult when one knows what a patient needs in the school setting,

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Zaida: Coordinating all services needed by patients and their family members; often requiring more than just a doctor’s appointment. Our international patients require very precise coordination and information for their visits to be a success. Our families are under much stress and in need of very specialized attention. It is also very difficult when you lose someone, for whom you have been coordinating care for many years. What are the most fulfilling aspects of your work? Dr. Thiele: Helping and making a difference. I think helping individuals with TSC and their families understand their disorder means a great deal. I also think we are getting better and better at treating the various manifestations of TSC, and hope strongly we are getting closer to preventive care. Anna: Getting to know patients at the Herscot Center is an immensely fulfilling part of my work. I am often deeply humbled by their generosity of spirit, strength, and hope in the midst of profound challenges. Relationships with patients and families, combined with the exceptional opportunity to work with the team at the Herscot Center as a medical student, has helped me to develop as a scientist and scholar and set the foundation for my career.

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Heidi: When initiation of dietar y therapy results of in seizure freedom. Margaux: Having the opportunity to interact with patients and families affected by TSC. Their courage, determination, and support of each other during difficult times has truly inspired

me and will continue to inspire me during medical school and throughout my career. Zaida: When our patients call back and are relieved the seizures have stopped and the person is making amazing gains that otherwise would not have

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s many people do at the end of one year and the start of another, I like to look back and reflect on what worked well and what did not and the changes to which I am looking forward. In 2011, I was thankful for what seemed like much progress being made in the way the TS Alliance serves its adult population. For instance, we launched the Adult Initiative and published a set of goals against which we can measure our future successes. T h e TS A lli an c e r e c o gnize d our efforts by dedicating funds to help us reach these goals. Accomplishing them will not be easy or quick and will continue to take the energy of many dedicated volunteers, both current and new, to realize them. This challenging environment is also evident at the Federal level. While the organization has enjoyed many successes over the last decade in receiving funds for medical research, it will take a redoubled effort in 2012 to allow the TS Alliance to continue to celebrate such successes in the years ahead. For those of you coming to Washington, DC in February to participate in the March on the Hill, we thank you. Whether you are an affected individual, parents or simply friends and relatives of persons whose lives are impacted by tuberous sclerosis complex in some way, your dedication is most appreciated. Beyond February there are several other new initiatives the TS Alliance is launching so stay tuned.

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happened. It is an incredible feeling to know you have made a difference in their lives. I think the best time of the year for me is November, when we start to receive the Christmas cards with family photos and you see the smiles on their faces. This lets you know they had a good year, and we did a great job.

B y Ke i th H all

2012 promises to be another exciting year for the TS Alliance and the adults and families it serves. There are so many opportunities available to those who have the time and inclination to help this organization grow. On behalf of the Adult Committee, I want to encourage you to get involved. Make this the year you volunteer to help coordinate a walk, the year you

,write your Congressman or Senator to ask for continued funding for TSC research, or the year you learn how to participate and enroll in a clinical trial. There are so many ways you can help. Explore www.tsalliance.org to find the opportunity that is right for you. For more information specifically on the Adult Initiative, contact Dena Hook at 800-225-6872 or [email protected].

Are You an Independent or SemiIndependent Adult with TSC? Please Join Us for Free Adult Informational Calls Call-in number: 866-613-5223 Access code: 4334003# Date:

Tuesday, February 9, 2012

Time:

8:00 P.M. EST, 7:00 P.M. CST, 6:00 P.M. MST, 5:00 P.M. PST (call length is 1 hour)

Topic:

How to Tell Your Friends/Employer About Your TSC

Presenters:

Pat Gibson, MSSW, ACSW

Date:

Thursday, March 15, 2012

Time:

8:00 P.M. EST, 7:00 P.M. CST, 6:00 P.M. MST, 5:00 P.M. PST (call length is 1 hour)

Topic:

Depression, Anxiety and TSC

Presenters:

Peter Newberry, MD

If you have questions or would like to receive handouts (if available) before the call, contact Dena Hook at [email protected] or 1-800-225-6872.

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Promising Science on the Possibility of Preventing Epilepsy

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he TSC Special Interest Group at the 2011 American Epilepsy S o c i e t y ’s A n n u a l M e e t i n g d i s c u s s e d p o s s ib l e ap p r o a c h e s for preventing the development of epilepsy in infants diagnosed with TSC prior to the onset of seizures. Although many questions remain to be answered, recent research is encouraging. Drs. Michael Wong and Sergiusz Jó´z wiak kindly agreed to summarize their presentations and discussions in the articles below. Dr. Wong discussed the potential role of mammalian target of rapamycin (mTOR) inhibitors in treating epilepsy in TSC, focusing primarily on the basic science rationale and pre-clinical studies. Dr. Jó´z wiak discussed relevant clinical data from a study in which treatment that was initiated after the onset of clinical seizures in some individuals but before the onset of seizures in others.

Michael Wong, MD, PhD, Washington University, St. Louis, Missouri Almost a decade ago, the two genes implicated in causing TSC—the TSC1 and TSC2 genes—were shown to inhibit the mTOR pathway, a biochemical pathway important in regulating cell growth and proliferation and many other important functions. As a result of TSC gene mutations, the activity of the mTOR pathway is abnormally increased, which likely accounts for increased cell growth and proliferation that causes tumor formation in TSC. Targeting this intrinsic biochemical abnormality, mTOR inhibitors have since been shown to decrease brain (subependymal giant cell astrocytomas, 16

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SEGAs) and renal (angiomyolipomas) tumor growth in TSC patients, leading to the recent approval by the US FDA of the mTOR inhibitor everolimus for treatment of SEGAs. The established efficacy of mTOR inhibitors for the treatment of tumors in TSC has raised the exciting possibility that mTOR inhibitors may also be beneficial for other disabling manifestations of TSC, in particular neurological symptoms such as cognitive impairment, autism, and epilepsy. There is now substantial pre-clinical evidence from multiple animal models of TSC that mTOR inhibitors may be effective for epilepsy. This includes both a decrease in seizure-frequency in mice that already have epilepsy, as well as potential “antiepileptogenic” actions in preventing epilepsy in presymptomatic mice. For example, in one mouse model involving inactivation of the Tsc1 gene primarily in astrocytes—a type of brain cell—early treatment of mice with rapamycin at a young age not only completely prevented the development of epilepsy, but also inhibited the underlying pathological, cellular, and molecular abnormalities in the brain that cause epilepsy. There are a couple of potential important applications of these findings from animal models of TSC for epilepsy. First, since many TSC patients have epilepsy that is poorly-responsive to traditional seizure medications, mTOR inhibitors could be considered as a mechanistically unique type of treatment for intractable epilepsy. Limited data examining seizures as a secondary outcome measure from one of the previous SEGA tumor trials from Cincinnati Children’s Hospital suggested that everolimus was effective

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in reducing seizures in a subset of TSC patients. In an ongoing clinical trial at Cincinnati and Baylor University in Houston that is specifically examining seizures as the primar y outcome, initial preliminary results also suggest that mTOR inhibitors may be effective for intractable seizures, at least for some TSC patients. However, there appears to be significant variability in the response of seizures to mTOR inhibitors; thus, completion of this and other clinical trials is needed before the role of mTOR inhibitors in treating intractable epilepsy in TSC patients can be definitively determined. In addition, given the apparent “antiepileptogenic” actions of mTOR inhibitors in preventing epilepsy in animal models of TSC, the possibility of treating TSC patients who are identified at a very young age to try to prevent the subsequent development of seizures, such as infantile spasms, has been considered. However, the potential adverse effects of early and long-term treatment with mTOR inhibitors in asymptomatic infants and young children is uncertain; thus, more basic science and clinical studies are definitely needed to determine whether a preventative treatment approach will be effective, safe, and feasible. Despite the current uncertainties and need for further research, there is a lot of excitement about the potential utility of mTOR inhibitors for epilepsy and other neurological manifestations of TSC.

Sergiusz Jó´zwiak, MD, PhD, Children’s Memorial Health Institute, Warsaw, Poland In his recently published study ( Euro p e an Jo urnal of Pe adiat ric

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Neurology, 2011; 15: 424-431), Dr. Jó´z wiak compared the neurocognitive outcome in 31 early diagnosed children who underwent treatment after onset of epilepsy (standard care group) with the outcome in 14 children who received antiepileptic treatment when their EEG became epileptogenic (before clinical seizures). All patients were assessed at 24 months of age. At this age, mental retardation was significantly more frequent and severe in the “standard” vs. the “preventative” group (48% vs 14%; p=0.031; mean IQ score 68.7 vs 92.3; p< 0.05). In the “standard” group, 10 out 31 (32.4%)  patients suffered from moderate, severe or profound mental retardation, while none of the

patients in “preventative” group had such significant developmental delay. The “preventative” group was also characterized by a higher ratio of seizure -free patients (93% vs. 35%; p=0.004), lower incidence of drug-resistant epilepsy (7% vs 42%; p=0.021), and fewer patients requiring therapy with more than one drug (21% vs 55%; 0.039) than the “standard” group. As the percentage number of patients receiving antiepileptic treatment was exactly the same (71%) in both groups, Prof. Jó´zwiak believes that all patients in the preventative group would have developed epilepsy if they had not been treated.  This study seems to confirm—for the first time on clinical grounds—the

results observed previously in animal models of epilepsy: that preventative antiepileptic treatment may significantly decrease incidence and severity of epilepsy in animals predicted to develop seizures. This therapeutic proposal is in concordance with some recently raised concepts of childhood epileptogenesis (Journal of Child Neurology, 2011;26:1411-21), demonstrating that in some genetic conditions, such as TSC, with a high probability of infantile seizure development, there is a latent period preceding the seizure onset. It is possible that therapeutic interventions during this latent period may avert some of the long-term sequelae of epilepsy such as persistent seizures and cognitive impairment. 

TS Alliance Announces New NYC Spring Event: Art for a Cure

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he New York Metro TSC community has a long track record of hosting a variety of successful fundraisers, including galas, food and wine events, and comedy nights. Now they have focused their talents on a more creative track--a brand new event called Art for a Cure. On April 29, from 2:00 pm – 4:30 pm at the Metropolitan Pavilion in New York City, we will gather to celebrate the artistic talent in our TSC community with an art exhibit and wine tasting. In keeping with the day’s theme, Dr. Steven Schachter, Professor of Neurology, Harvard Medical School, and Editor-in- Chief of Epilepsy & Behavior magazine, will make a featured presentation about the day-today aspects of epilepsy, including how artwork and music can inspire research because they underscore the perspectives of people affected by epilepsy. Dr. Schacter will play

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an accompanying slideshow of artwork from his reknowned Brainstorms series. The ar t to be shown during the exhibit will be collected from a nationwide competition held by the TS Alliance. The art contest will be officially announced on the TS Alliance website and other social media outlets on February 1, 2012. Contestants will have one month to create their works of art and display them online. Individuals of all ages living with TSC are eligible and encouraged to enter. Artists will be divided into three categories: 1 – 11 years of age, 12 – 20 years of age, 21 and older. Any medium of art may be used as long as it can be displayed online for voting purposes. Voting starts March 1 and runs through April 12. Each vote is $5 and benefits the TS Alliance. Prizes will be given to the top vote getters in each age category. After the contest, all entries

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will be required to be shipped to New York City, where they will be on display and for sale during the Art for a Cure event, which will also feature live and silent auctions. The winners in each categor y will be announced during the event. EHE International has also generously donated use of its retail/display window located at Rockefeller Plaza throughout May 2012. The TS Alliance will use the display to promote awareness of our organization and TSC, highlight TSC Awareness Month and recognize the overall winning entry from the art contest. Sponsorships are available from $1,000 to $15,000 and individual tickets will sell for $75. For more information on the event or to join our committee, please contact Linda Gorsuch, Senior Director of Development, at lgorsuch@ tsalliance.org or 800.225.6872.

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Honorariums (August 2011–December 2011) You can honor a friend or family member for an important occasion with a gift to the TS Alliance. It is a wonderful way to send a birthday or anniversary wish, or congratulations for retirement, a job well done, graduation, etc. Please include the name and address of the individual being honored so that acknowledgement of your kind donation can be sent. Tuberous Sclerosis Alliance honorarium cards are also available if you would like to make a gift in honor of family, friends, or colleagues. To receive tribute cards, call Tye Hoffman at (240) 638 4643 or by email at [email protected]. Tribute(s) for Sean Aaberg Mr. and Mrs. Jeffrey Aaberg Tribute(s) for Henry Albers Mr. and Mrs. James S. Tart Tribute(s) for Rocco Alex Mr. and Mrs. Rocco Spinoso Tribute(s) for Ronalie Alonzo Ms. M. Sievers Tribute(s) for Alan A. Anderson Mrs. Cyndy Chesney Tribute(s) for Brian P. Anderson Mr. and Mrs. Paul H. Anderson Tribute(s) for Christopher D. Anderson Ms. Carol L. Anderson Tribute(s) for Reese Annen Cane’s Chicken Fingers Tribute(s) for Bladen D. Arndt Mr. Ernest Bailey Ms. Dianne Kirschke Mrs. Darlene Yee Tribute(s) for Tommy Barker Ms. Sandra M. Beckwith Tribute(s) for Xavier Barr-Malec Mr. and Mrs. Robert E. Newlin Mr. and Mrs. Donald Peaslee Tribute(s) for John R. Beattie Dr. and Mrs. Thomas W. Beattie Tribute(s) for Joshua P. Beck Ms. Gloria C. Beck Ms. Karen White Tribute(s) for Daniel Beldner Mr. and Mrs. Stuart Marton Tribute(s) for Jonathan B. Berger Mr. and Mrs. Jules Reich Tribute(s) for Bessire & Casenhiser, Inc. Mr. Michael W. Mihelich Tribute(s) for Jacob Blood Dr. Scott W. Arndt Mr. and Mrs. William S. Blood, Sr. Mr. and Mrs. Frederick A. Curylo Mrs. Cynthia M. Gillette Mrs. Melissa K. Harvey Mr. and Ms. Albert A. Ricchetti Mr. and Mrs. Kurt Wagner Tribute(s) for Kristen A. Bloomfield Mr. and Mrs. Edward J. Bloomfield Tribute(s) for Elyse Bodiford Mr. and Mrs. Danny Bodiford Mr. and Mrs. Gerald W. Hooper Tribute(s) for Matt W. Bolger Mr. William Bolger Mr. and Mrs. David A. Krinsky Tribute(s) for Rachel Bolger Mr. and Mrs. William A. Brown Tribute(s) for Chloe Bredeson Mr. and Mrs. Alan R. Coyne Tribute(s) for Anthony Brewer Ms. Devekka Cook Ms. Julia Crupi Ms. Judith M. Demuro Mr. and Mrs. Robert H. Gill Ms. Amy Moore Mr. Roel Schrijer Mr. Robert J. Yankanin

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Tribute(s) for Bo Breymeier Ms. Cynthia A. McGraw Tribute(s) for Alexa Brown High Beam Electric Corp Mr. and Mrs. Edward A. Kalman Mr. and Mrs. Vito Lopa Tribute(s) for Susie Brown Mr. and Mrs. Thomas Goetz Tribute(s) for Daniel L. Buchsbaum Mr. and Mrs. Andrew Buchsbaum Tribute(s) for Dennis Busel Mr. and Mrs. Harvey J. Busel Tribute(s) for Anne Buzzy Mr. Joseph Rotellini Tribute(s) for Katrina Caban Mr. Mark Salvaggio Tribute(s) for Matthew Campbell Mr. Bernard P. Kavanagh Ms. Courtney Oei Tribute(s) for Nathan P. Carroll Mr. and Mrs. John R. Carlson Mr. and Mrs. Liam Carroll Tribute(s) for Laura Cates Ms. Sue Catlett Tribute(s) for Frank Cenna Ms. Elizabeth B. Mahon Mr. and Mrs. Mark M. Peterson Tribute(s) for Cindy Chernow Mr. Donald Fowler Tribute(s) for Nicholas P. Chess Mr. and Mrs. Daniel Chess Mr. and Mrs. Michael F. Scaliti Tribute(s) for Elizabeth A. Christensen Ms. Kim R. Armstrong and Ms. Joyce C. Armstrong Tribute(s) for George C. Christensen Ms. Kim R. Armstrong and Ms. Joyce C. Armstrong Tribute(s) for Susan Christensen Ms. Kim R. Armstrong and Ms. Joyce C. Armstrong Tribute(s) for Brooks Clarkson Mr. R.B. Eddins Tribute(s) for Liam M. Coady Mr. and Mrs. Thomas J. Coady Ms. Bridget C. Daly Tribute(s) for Kama A. Coates Ms. Yovanda L. Coates Tribute(s) for Chloe Coil Ms. Judy Ackers Tribute(s) for Bailey Cole Mr. and Mrs. Barry C. Visioli Tribute(s) for Tyler Cole Mr. and Mrs. Lars Cole Tribute(s) for Joey Conger Mr. and Mrs. Kent Ferris Tribute(s) for Maggie Conner Ms. Jane A. Angle Tribute(s) for Charlie Cowlin Ms. Aura Day Tribute(s) for Tommy Cox Mr. and Mrs. Charles L. Anderson Tribute(s) for Bella Davis Dr. Adrian Banner

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Tribute(s) for Law Davis Mr. and Mrs. Larry J. Davis III Mr. and Mrs. Jimmy Hill Tribute(s) for Dane Dawson Mrs. Emily Schwab Mr. and Mrs. Francis J. Singer Mr. Scott Singer Tribute(s) for Mary Day Mrs. Anne Day Tribute(s) for Cole Denharder Mr. and Mrs. Cornelius Denharder Mr. and Mrs. Ronald Oakes Tribute(s) for Jacob E. Dickison Mr. and Mrs. John G. Torkelson Tribute(s) for Steven M. Dills Mr. and Mrs. Michael Gutto Tribute(s) for Alexandra Donato Ms. Linda Hill Ms. Carolyn Nesbit Mr. and Mrs. Glenn Wegryn Tribute(s) for Conrad L. Duprez Dr. Rand Cottle Tribute(s) for Judy Duprez Dr. Rand Cottle Tribute(s) for Caleb Elston Ms. Theresa Long-Staples Tribute(s) for Lauren Emge Mrs. Janet Emge Tribute(s) for Bill Ennis Mr. and Mrs. Frances Mulvey Tribute(s) for Kim Feldmeyer Mr. and Mrs. Thomas Goetz Tribute(s) for Layne Feltenberger Mrs. Jessica Feltenberger Mrs. Gale Law Tribute(s) for Andy Fisher Mr. and Mrs. Frances Mulvey Tribute(s) for Dan Fisher Mr. and Mrs. Frances Mulvey Tribute(s) for Helen Fisher Mr. and Mrs. Frances Mulvey Tribute(s) for Jim Fisher Mr. and Mrs. Frances Mulvey Tribute(s) for John D. Fisher Mr. and Mrs. Frances Mulvey Tribute(s) for Pat Fisher Mr. and Mrs. Frances Mulvey Tribute(s) for Peggy Fisher Mr. and Mrs. Frances Mulvey Tribute(s) for Tom Fisher Mr. and Mrs. Frances Mulvey Tribute(s) for John W. Fitzmaurice Anonymous Ms. Courtney Abby Ms. Leslie S. Abrams Mr. Sean Bamman Mr. Evan Baumgarten Mr. and Mrs. Bob Biegel Mrs. Rosemary Brennan Mr. Daniel Brestle Mr. Kevin Carey Mr. Stanley Chiu Miss Caroline Cluzel Mrs. Susan Coppola Mr. Angelo Coppolino Mrs. Judy Cosgrove

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Mr. Michael Cramer Mrs. Jeanne Curran Mrs. Allison Dalessandro Mr. James Daniello Mrs. Noelle Davison Mrs. Angelica Degenaars Mrs. Teresa Delmonico Mrs. Sara Deren Mr. L. DeVencentis Mr. and Mrs. Evan DeWitt Mrs. Erin Dwyer Mrs. Laura Feeley Ms. Kathy Fernandes Mr. Brian Feury Mr. and Mrs. Bruce Fitzmaurice Mrs. Kelly Flanagan Mr. and Mrs. Ronald Frederick Mr. Edward Galenkamp Mr. Jesse Gellrich Ms. Stephanie Giardino Mr. Thomas Granatell Ms. Laura Gruber Mrs. Theresan Guiney Mr. Scott Haggerty Mrs. Melissa Harris Ms. Susan M. Healion Mr. Kevin Heck Mrs. Alison Ismael Mr. Steve Johnson Mr. Charles Kaetz Mrs. Deanna Kirchner Mr. Ted Kramer Mr. and Mrs. Christopher Langbein Ms. Stephanie Langbein Mr. and Mrs. Thomas Langbein Mrs. Kathleen Leiz Mr. Bernard Leone Mr. Matt Leone Mr. Anton Levy Mrs. Edna Lewitz Mr. Michael Lieberman Mr. Jeremy Liebhoff Mr. Christopher M. Mahony Mr. Michael Mainwald Mrs. Janice Maloof Mr. Louis Mari Mrs. Toni McAlevey Medco Health Solutions Charitable Match Fund Mr. Frank G. Monks Mr. Eric Morgan Ms. Barbara Nastro Ms. Autumn Nero Mrs. Laurie Nieves Mr. Liam O’Connell Ms. Tracy Parker Mr. Christopher Pernetti Ms. Toni Pernetti Mrs. Sally B. Ponchak Mrs. Rosa Quartuci Mr. Martin Raborn Mr. Matthew Raskin Mr. Jesung Ryu Ms. Lynn M. Samuel Mr. Dennis Scully

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Mr. Thomas Sheeran Mr. Richard Slaughter Mrs. Kristin Stefankiewicz Mr. Robert Trause Mr. Jonathan Tsui Mrs. Nancy Whitman Mr. Robert Wieck Ms. Rebecca Wright Mr. Alan Zaret Mr. Joseph Zerillo Mrs. Silvia Zicherman Tribute(s) for Mathew Flaherty Mr. and Mrs. Joseph Anthony Tribute(s) for Patrick Flaherty Mr. and Mrs. Joseph Anthony Tribute(s) for Sophia Flicker Sales Northwest Inc. Tribute(s) for Judy Franco Mrs. Judy Franco Tribute(s) for Alex Gershon Ms. Nancy L. Gershon Tribute(s) for Martha Goetz Mr. and Mrs. James C. Cammack Tribute(s) for Tiara Goff Mr. and Mrs. Paul Altieri Tribute(s) for Mike Gohl Mr. and Mrs. Barry K. Retchloff Tribute(s) for Meagan Golden Mr. and Mrs. Arnold I. Weinstein Tribute(s) for Ann C. Gordey-Backus Anonymous Tribute(s) for Robert Grandia Mr. Ernest Schroer Mr. and Mrs. J. C. Strutzel Tribute(s) for Shannon Grandia Mr. Ernest Schroer Mr. and Mrs. J. C. Strutzel Tribute(s) for Jared Greytock Mrs. Myrtle M. Jantzi Tribute(s) for John David Grimes Arkansas Community Foundation Tribute(s) for Trey Gwinn Bank of America Mrs. Taylor Florence Tribute(s) for Jade C. Hahn Ms. Alison R. Wroblewski Tribute(s) for Thomas Hammerquist Mr. Charles B. Whiteside Tribute(s) for Abby Hase Mr. and Mrs. Michael Wood Tribute(s) for Anna Hathaway Mr. and Mrs. James J. Santos, Jr. Tribute(s) for Bao Heffron Mr. Kelly J. Barnes Tribute(s) for Hannah Henke Deborah Schaefer Tribute(s) for Shawn Higgins Mr. and Mrs. Robert E. Higgins, Jr. Higgins Mobile Homes, Inc. Mr. and Mrs. Robert E. Higgins Tribute(s) for Mathew Hillier Mr. and Mrs. Lewis F. Lipkin Mrs. Jean H. Whittingham Ms. Patricia Zak-Kearon

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Tribute(s) for Elise Hoersch Mr. and Mrs. Jeffrey S. Hoersch Mr. Jon F. Myers Tribute(s) for Robert M. Hoffmann Mr. and Mrs. Jeffrey Hoffmann Tribute(s) for Emily M. Holinka Mr. and Mrs. Glenn Kenney Tribute(s) for Sam Hopkins Mr. and Mrs. Jason A. Mitchell Tribute(s) for Hannah L. Hoslet Mr. and Mrs. William H. Dabbs Tribute(s) for Sarah Hulse Mr. and Mrs. Allen Bernard Tribute(s) for Karlie J. Hutchins Mrs. Margaret L. Spiewak Tribute(s) for Benjamin Hutchinson Mr. and Mrs. Michael S. Richards Dr. Julie Smail Tribute(s) for Alison B. Hyman Ms. Karen Thomson Tribute(s) for J & H Asset Property Management, Inc. Mr. Michael W. Mihelich Tribute(s) for Kevin Jackson Greater Miami Jewish Federation Tribute(s) for Carter J. Janowicz Mr. and Mrs. Joseph Janowicz Tribute(s) for Hannah Jeffers Mr. and Mrs. Keith A. Gaskill Tribute(s) for Sara M. Johns Mrs. Imogene Johns Tribute(s) for Annie Johnson Anonymous Mr. and Mrs. David S. Alden Altalib Family Limited Partnership Mr. Philip M. Anders Ms. Grace Aquino Ms. Dolores Berglund Mr. and Mrs. Clarence Bielawski Mr. and Mrs. Kenneth Boehm Mr. and Mrs. Peter A. Bogatyr Mr. and Mrs. Elliott P. Brownstein Mr. and Mrs. Ray Burns Mr. and Mrs. Allan S. Chandler Ms. Toba Chrein Mr. and Mrs. Steven Cooper Mr. and Mrs. Rick A. Del Mastro Mr. Andres M. Fernandez Ms. Ellen C. R. French Mr. and Mrs. James W. Gilley Mr. and Mrs. Carl L. Godman Mr. and Mrs. Robert Graham Mrs. Patricia A. Grange Mr. and Mrs. Robert W. Groves III Mr. and Mrs. Gordon E. Harvey Mr. and Mrs. Jim Hauck Mr. and Ms. Oscar Haynes Mr. and Mrs. Frank Holzman Mr. and Mrs. Henry J. Hribar, Jr. Mr. Bruce Janovsky Mr. and Mrs. Lawrence C. Johnson Mr. and Mrs. Ken Johnson Ms. Sally K. Jones Mr. and Mrs. Arnold W. Kamm Mr. and Mrs. Robert Kanne Mr. and Mrs. Gary J. Katz

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Mr. and Mrs. James W. Krueger Mr. and Mrs. Wayne D. Kuhn Mr. and Mrs. Walter P. Lysaght Mr. and Mrs. James C. Malone Mr. and Mrs. Patrick J. Marshall Mr. and Mrs. James F. Mulcahy Mr. and Mrs. Kenneth R. Plum Mr. and Mrs. Gerry J. Riemersma Mr. and Mrs. Carleton F. Rosenburgh Mr. and Mrs. Steve Schroffel Mr. and Mrs. Marvin Singer Mr. and Mrs. James J. Slattery Ms. Frances P. Strassman Mr. and Mrs. Bill D. Sturm Mr. and Mrs. Tibor Taraba Mr. and Mrs. Boyd Van Ness Mr. and Mrs. Perry C. Vascellaro Mr. and Mrs. Ron K. Vickrey Mr. and Mrs. Jared D. Willcox Mr. Glen T. Wilmes Mr. and Mrs. W.N. Young Tribute(s) for Ken Johnson Mr. Patrick R. Dolan Fairway Services Group Mr. Dennis Hanson Illinois Insurance Center Mr. and Mrs. William T. Redgate II Tribute(s) for Shonnie Johnson Mr. Patrick R. Dolan Fairway Services Group Mr. Dennis Hanson Illinois Insurance Center Mr. and Mrs. William T. Redgate II Tribute(s) for Raymond A. Julow Mr. and Mrs. James R. Julow Tribute(s) for Kendall Kesig Mr. and Mrs. Gary Kesig Ms. Marilyn Swisher Tribute(s) for Samantha Kieny Mr. and Mrs. Thomas J. Reimann Tribute(s) for Grace Kisselburgh Ms. Esther Ash Tribute(s) for Nathan A. Kliebert Mrs. Kim Cannon Tribute(s) for Joseph M. Klinger SanMar Corporation Tribute(s) for Georgia Kness Ms. Ruth W. Aubey Tribute(s) for Lee Kness Ms. Ruth W. Aubey Tribute(s) for Crystal Knotts Mr. and Mrs. David M. Serrone Tribute(s) for Jackson Kozisek Mr. Barry L. Allen Tribute(s) for Cathy J. Krinsky Mr. Mac Robinson and Ms. Lyn Krinsky Mr. James M. Robinson Dr. and Mrs. Robert E. Simon Tribute(s) for Lauren E. Krinsky Ms. Eva Monastersky Tribute(s) for Melissa Kulik Mr. and Mrs. Alex Kulik Tribute(s) for Thomas Langbein Mr. and Mrs. Bruce Fitzmaurice Tribute(s) for Jude Langstaff Mrs. Pamela Taupier Tribute(s) for Alison Lawless Ms. Kathleen Djenfer Tribute(s) for Catherine Lawless Ms. Kathleen Djenfer Tribute(s) for Paul Leist Mr. and Mrs. Robert Boehner Ms. Nicole Mountel Mr. and Mrs. Robert S. Nyswonger Mr. and Mrs. William M. Roebel

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Mr. and Mrs. Chestine Spence, Jr. Tribute(s) for Caroline Leonard Ms. and Mrs. Chris P. Lavanchy Tribute(s) for Jared Levine Mr. and Mrs. Kenneth S. Jaffe Tribute(s) for Lauren Levine Mr. and Mrs. Jonathan Myers Tribute(s) for Patrick Lewis Ms. Mary E. Lewis Tribute(s) for Kacy K. Lias Mrs. Barbara T. Lias Tribute(s) for Josephine Liddle Ms. Susan Jones Tribute(s) for Tommy R. Lindsey Mr. and Mrs. Richard I. Carp Tribute(s) for Hannah Linsin Mrs. Muriel Pattis Mr. Donald W. Schaumberger The Herbst Foundation Tribute(s) for Vicki Long Anonymous Tribute(s) for Anthony Lucenti Mrs. Theresa Murphy Tribute(s) for Haley N. Lynch Capt. Joseph Daugherty Mr. and Mrs. Jerry Short Tribute(s) for Phillip Macri Capt. and Mrs. Roger Wilson Tribute(s) for Katie Madea Ms. Nancy B. Welch Tribute(s) for Wendy Madea Ms. Nancy B. Welch Tribute(s) for Madelyne Majors Ms. Shirley G. Esquith Tribute(s) for Emily Masterman Ms. Beverly L. Bishop Tribute(s) for Genie Matthews Mrs. Julia D. Webb Tribute(s) for J. Payson Matthews Mr. and Mrs. Ray McGhee Mrs. Amy Winfrey Tribute(s) for Megan Mauro Mr. and Mrs. Steve Mauro Tribute(s) for Riley Mayhew Anonymous Tribute(s) for Sophia Mayrsohn Mr. and Mrs. John Nolan Tribute(s) for Allen McBride Mr. Herndon Rouse Tribute(s) for Robert E. McBride Mr. and Mrs. John McBride Tribute(s) for Robynn McCall Mr. and Mrs. Michael McCall Tribute(s) for Ashlin McFadden Mr. and Mrs. Charles McFadden Tribute(s) for Roy Mechler Mr. and Mrs. Dennis Vertrees Tribute(s) for Yvonne C. Melvin Mr. and Mrs. Gary L. Caldwell Tribute(s) for Priscilla Middleton Mr. and Mrs. Robert H. Middleton Tribute(s) for Davya Miller Ms. Sally R. Parry Tribute(s) for Lainey Miller Mr. Daniel Perkins Tribute(s) for Makai Milton Mr. and Mrs. Peter L. Monkmeyer Tribute(s) for Nadra Mlynarczyk Mr. and Mrs. Richard D. Olson Mr. and Mrs. Clayton E. Spence Tribute(s) for Lindsay Moody Anonymous Tribute(s) for Katie Munneke Mr. and Mrs. Dennis Landis Tribute(s) for Annika Ng Ms. Elaine Bowers

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Tribute(s) for John “Thorpe” T. Richards Mr. and Ms. David H. Solomon Tribute(s) for Thorpe Richards Mr. and Mrs. Robert Perry Tribute(s) for Zoey Richter Mr. and Mrs. Eugene D. Zimmerman Tribute(s) for Sidney Rouse Mr. and Mrs. Douglas E. Anderson Mr. Jarvis L. Cain Mr. Sydney D. Christopher Mr. and Mrs. Ron Smith Tribute(s) for Grace Rubeck Mr. David J. Diluciano Mr. and Mrs. Tyler Stevenson Tribute(s) for Daniel J. Russo Anonymous Tribute(s) for Leielle Saddik Mr. and Ms. Mel Chaifetz Tribute(s) for William V. Sadoski Ms. Raenette M. Kramer and Ms. Leticia A. Posk Tribute(s) for Ella M. Sanders Ms. Mildred M. Sanders Mr. Todd Zebert Tribute(s) for Irl Sanders Mr. William Ashford-Malcomson Mrs. Lisa Lukas Palisades Music Studio Mr. Jon Schell Tribute(s) for Marni Sanders Mr. William Ashford-Malcomson Mrs. Lisa Lukas Mr. Jon Schell Tribute(s) for Christian I. Santos Mrs. Sylvia M. Sparby Tribute(s) for David P. Schenkein Dr. and Mrs. David P. Schenkein Tribute(s) for Madalyn Scherer Mr. and Mrs. Peter A. Cari Dr. and Mrs. Verne E. Cowles Mr. and Mrs. Joseph D. Garvey Mr. and Mrs. Andrew M. Jaeger Mr. and Mrs. Michael Schneider Tribute(s) for Francesca Schmidt Palmer Family from Oz Tribute(s) for Stephen F. Schmitt Mr. and Mrs. William Schmitt Tribute(s) for Greyson R. Schwaigert Anonymous TASC Western Region Group Sales Team Tribute(s) for Mary A. Scroggins Mr. and Mrs. Gilbert Mackey Waukegan Tire Tribute(s) for Kylie Seggerman Mr. and Mrs. Bob Glick Tribute(s) for Robert A. Seymour Mr. Randy Elkinson Tribute(s) for Benjamin Shapiro Anonymous Mrs. June J. Bardwil Mr. and Mrs. Joseph P. Harris Ms. Milvi Laan Mr. Max McGinley Mr. and Mrs. Tom Todaro Tribute(s) for Meghan J. Sirinek Mr. Thomas Krieg Mr. and Mrs. Robert Pfeiffer Tribute(s) for Charlotte Skillin Mr. and Mrs. Mark D. Andrews Ms. Anne L. Skillin Mr. and Mrs. Christian Skillin

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Tribute(s) for Drew Sklarin Ms. Pearl Shapiro Tribute(s) for Olivia Smiley Mr. and Mrs. Robert E. Apple, Jr. Mr. Robert E. Apple, Sr. Mr. Chris Calhoun Constellation Brands U.S. Mr. Emanuel C. Hoover Insulation Products Corp Ms. Helen Kastrenakes Mr. and Mrs. Jay Smiley Tribute(s) for Shae Sunahara Mrs. Lori Nash Tribute(s) for Emily B. Szilagyi Ms. Doris R. Childs Tribute(s) for Seth Taylor Ms. Abigail M. Taylor Tribute(s) for Will Taylor Mr. and Mrs. David A. Custer Mr. and Mrs. Mark Fryer Mrs. Megan McCloskey Mr. and Mrs. Jay Weidenbaugh Tribute(s) for Benjamin Theis Mr. and Mrs. Paul Thomas Tribute(s) for Elizabeth A. Thiele Arlyn J. Roffman Tribute(s) for Cathryn Tilley Mr. and Mrs. Jack E. Tilley Tribute(s) for Tyler J. Trapp Mr. and Mrs. Donald Hauge Tribute(s) for Ashley Triemer Mr. and Mrs. William L. Triemer Tribute(s) for Andrew R. Trundle Mr. and Mrs. Randy E. Hazard Tribute(s) for Makenna G. Turner Mr. Thomas Eiben Tribute(s) for Kurt T. Ullrich Ms. Anita Ullrich Tribute(s) for Benjamin M. Valdez Mr. and Mrs. Richard L. Keister Tribute(s) for David Wangness Mrs. Barbara Montgomery Tribute(s) for Lise Wangness Mrs. Barbara Montgomery Tribute(s) for Jeb Ward Mr. and Mrs. T. Robert Ward Jr. Tribute(s) for Eli Warner Mr. and Mrs. Warren G. Stauffer Jr. Mrs. Shannon Warner Tribute(s) for Lindsey E. Wilson Mr. and Mrs. Thomas Engle Tribute(s) for Ronald Witt Mr. and Mrs. Frances Mulvey Tribute(s) for Tyler Wooer Mr. and Mrs. James D. Mitchell Tribute(s) for Heather M. Wright Mr. Ted Waldron Tribute(s) for Beverly J. Xavier Mr. and Mrs. Ken Johnson Tribute(s) for Colin Yokoyama MW Group Ltd Tribute(s) for Tavi Yokoyama MW Group Ltd Tribute(s) for Alyssa Youmans Mr. Scott Allensworth and Ms. Amy Allen Ms. Veronica H. Ancy Mr. Larry Angus Mr. and Mrs. Arthur A. Antiporda Ms. Christina Baik Mr. Michael E. Bailey Mr. and Mrs. Tom Beyer Ms. Andrea Bracken Ms. Debra Bracken Mr. and Mrs. Travis Branam

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Mr. and Mrs. Michael D. Breen Ms. Mary L. Cady Ms. Luellen Casler Colorado Consulting Services Inc. Mr. Richard S. Croushore Mr. and Mrs. G. C. Davenport Ms. Linda M. Davis Mr. and Mrs. Randy S. Dirks Mr. and Mrs. William S. Finley Mr. and Mrs. Michael F. Flynn Ms. Suzann S. Foord Ms. Marjorie Frahlich Mr. Joel S. Fredrickson Mr. and Mrs. Douglas C. Fuit Mr. and Mrs. Glenn T. Gaffney Mr. and Mrs. Thomas S. Gaffney Mr. and Mrs. David E. Glass Mr. and Mrs. Rex L. Glass Mr. and Mrs. John W. Goff Mr. and Mrs. Gary W. Gressett Mr. and Mrs. Kenneth G. Grimes Mr. and Mrs. William S. Grubb Mr. and Mrs. Walter G. Henke Ms. Sherry A. Hike Ms. Beth Hubbard Ms. Joyce J. Hyden Ms. Lynn M. Isham Mr. and Mrs. David M. Janssen Mr. and Mrs. George T. Keyes Mr. and Mrs. Tim Kilgannon Ms. Diane Klinkerfues Mr. and Mrs. James P. Konrad Mr. Jeffery S. Kramer Mr. and Mrs. David L. Kruse Mr. and Mrs. James Larson Ms. Marilyn E. Lembcke Mr. and Mrs. James C. Lockhart Mr. and Mrs. Joe H. Martin Mr. and Mrs. Stephen R. Mason Mr. and Mrs. Douglas C. Moore Mr. and Mrs. David M. Mumaugh PASCO Mr. and Mrs. Rory T. Peachey Mrs. Rosalyn Reese Mr. and Mrs. Michael A. Rentos Mr. and Mrs. Philip P. Rhodes Mr. and Mrs. R. Rimbert Ms. Jennifer L. Roswell RT Auto & Truck Repair LLC Mr. and Mrs. David D. Sanders Mr. and Mrs. Lorne M. Sedlacek Dr. and Mrs. Floyd T. Sekiya Shawn Gaffney Memorial Fund Ms. Mari M. Skora Mr. and Mrs. Douglas H. Smith Ms. Kathleen J. Smith Mr. and Mrs. Michael H. Sommer Mr. James O. Thompson Mr. and Mrs. Otto Wilson Mr. and Mrs. Gerald P. Youmans Mr. and Mrs. Roland Youmans Mr. and Mrs. Rexford D. Youmans Mr. and Mrs. Stanley R. Youmans Mr. Mark S. Zimmer Tribute(s) for John Zarbetski Harrison East Newark Elks #2326 Ms. Elizabeth McInnis Tribute(s) for Paul Zarbetski Harrison East Newark Elks #2326 Ms. Elizabeth McInnis Tribute(s) for Emma Zeidman Ms. Eileen M. Keely Tribute(s) for Delanie M. Zimmer Mr. Michael P. Smith

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Memorials (August 2011–December 2011) Contributions are given to the Tuberous Sclerosis Alliance at the request of family members in memory of their loved ones. We extend our sympathies to the family and friends of those memorialized below. These generous contributions support the progress of our mission to find a cure for tuberous sclerosis complex. Dr. Martin I. Golding and Ms. Melissa

Mr. and Mrs. Stanley Smith

Tribute(s) for Sherril Ann

Richmond Motor Sales

Ms. Lucy Brody

Mrs. Audrey Malesky

Mr. and Ms. Richard A. Rymer

Ms. Ann M. Garfinkle

Tribute(s) for Robert S. Baranowski

Mr. Steven Scuderi

Mr. and Mrs. David Gurowsky

Mr. and Mrs. John L. Heithaus

Mr. and Mrs. Paul Wolfenbarger

Ms. Carolyn Baranowski

Susan M. Smith

Mr. and Mrs. Richard Heilman

Mrs. Julie H. Ilkovich

Tribute(s) for Francine L. Ostrow

Tribute(s) for Jake Barash

Mr. and Mrs. Larry A. Stevens

Ms. Rita Segerman

Mr. and Mrs. Matt Jorski

Mr. and Mrs. Andrew Buchsbaum

Ms. Lisa Hernreich

Mr. and Mrs. Edward A. Streed

Ms. Arlene J. Swartz

Ms. Rhonda Kabat

Mrs. Norma Ehrlich

Mr. and Mrs. Steven Mullens

Mr. and Mrs. William W. Sultan Jr.

Tribute(s) for Cynthia R. Holman

Ms. Catherine Kadar

Tribute(s) for Norman E. Patrick

Mr. and Mrs. Ellis Sostrin

Ms. Maelyn M. Thornton

Ms. Lois Pariani

Ms. Carol Keating

Mr. and Mrs. Robert N. Mayer

Tribute(s) for Cindy Barnard

Ms. Shirley A. Westerlund

Tribute(s) for David Howell

Ms. Hillary Klein

Mr. and Mrs. Ralph Roesler

Ms. Carol D. Hobart

Mr. and Mrs. Darrell Wiatrowski

Mr. and Mrs. James R. Trimm

Mr. and Mrs. David A. Krinsky

Tribute(s) for Margaret Ramsey

Tribute(s) for Jack Beard

Tribute(s) for Williams P. Burke

Tribute(s) for Grace L. Hyatt

Lt. Alexei Kudla

Mr. and Mrs. Earlby Ramsey

Mr. and Mrs. Andy M. Becker

Mr. and Mrs. Donald Hauge

Ms. Janet Bozeman

Ms. Henrietta Kundert

Tribute(s) for Mary Riffel

Mr. Chris P. Kelly

Tribute(s) for Sherrie Busel

Tribute(s) for Leonora K. Kahlen

Mr. Irving Liebowitz

Ms. Audrey V. Bukowski

Mr. Harold M. Martin and Ms. Marie

Mr. and Mrs. Richard A. Daniels

Ms. Darlene M. Hall

Lisa W. Gill Trust

Tribute(s) for Rosemary Schwaigert

Tribute(s) for Dusty A. Choate

Ms. Anneliese M. Langen

Dr. Andrew V. Panagos

Anonymous

Mr. and Mrs. Robert C. McCann, Jr.

Anonymous

Mr. and Mrs. Erik S. Monsen

Preop Holding Suburban Hospital

Ms. Betty S. Bower

Mrs. Tina Pelino

Mr. and Mrs. Steven Dodson

Mr. Ferdinand J. Nowak

Mr. and Mrs. John T. Richards, Jr.

Mr. and Mrs. John O. Cade II

Mr. and Mrs. David Remer

Mrs. Deborah Higgins

Mr. and Mrs. James A. Pate

Ms. Mildred H. Robins

Mr. Robert E. Sickler

Ms. Sandra H. Sontag

Mr. and Mrs. Mitchell C. Jones

Mrs. Jean Pudwill-Kelley

Mr. and Mrs. Christopher Rosbeck

Tribute(s) for Adam G. Scott

Ms. Lorene M. Wheeler

Ms. Barbara Marcum

Tribute(s) for Andrea Kebbel

Dr. Steven Scholl

Mary Ellen Scott

Tribute(s) for Barbara Belanger

Ms. Nancy Smithen

Dr. and Mrs. and Ms. Augustine

Mrs. Carole Stevens

Tribute(s) for Juliana Seaman

Mr. and Mrs. Herbert G. Schurian

Tribute(s) for Raymond D. Conner

TSC Canada

Mr. Robert K. Bycroft

Tribute(s) for Neva Berweiler

Mr. and Mrs. Robert Bonness

Mr. and Mrs. Robert Meyer

Mr. and Mrs. Neil L. Willens

Tribute(s) for Timothy L. Strickley

Ms. Barbara Pitney

Mr. and Mrs. William D. Conner

Mr. and Mrs. John T. Sciano, Sr.

Mr. Jeffrey Zell

Ms. Roberta Hirt

Tribute(s) for Heather J. Buntrock

Ms. Edith Greenstone

Tribute(s) for Svetlana Kleyner

Tribute(s) for Madolyn Measel

Tribute(s) for Walter F. Stromek

Mr. and Mrs. Harry R. Allen

Mr. and Mrs. Carey Michael Phillips

Ms. Deborah Gershner

Mrs. Karen Blount

Ms. Patricia J. Becker

Mr. and Mrs. Damien L. Amore

Mr. and Mrs. James B. Phillips

Mrs. Fylise Goldfarb

Tribute(s) for Patricia B. Miller

Mrs. Tina Calich

Ana Ventures, Inc

Mr. and Mrs. Kenneth A. Slavens

Mr. and Mrs. Michael Rosenblatt

Ms. Sandra M. Beckwith

Mr. Christopher Furlong

Mr. and Mrs. William M. Anderson

Todd Family Charitable Foundation

Tribute(s) for Kitty Kulesza

Ms. Arlene Mencke

Ms. Lauren Lavezzi

Mr. and Mrs. J. McNeill Anderson

Mr. and Mrs. Michael C. Ziemba

Mr. and Mrs. Dwight V. Nunnelley

Tribute(s) for James M. Moody

Mr. and Mrs. Lawrence J. Lavezzi

Mr. and Mrs. Nathan D. Ansell

Mrs. Yvonne Ziemba

Tribute(s) for Stanley T. Lasonczyk

ACC Construction Company, Inc.

Mr. Robert H. Moll, DDS

Aquanut Water Shows, Inc.

Tribute(s) for Richard Connors

Mr. and Mrs. Thomas Engle

Ms. Pamela G. Hadsell

Mr. and Mrs. Robert Puoci

Ms. Carol A. Awe

Ms. Linda G. Connors

Tribute(s) for Lisa Levey

Mr. and Mrs. Michael W. Jennelle

Mr. and Mrs. Kenneth Wyer

Bassett Auto Repair, Inc.

Tribute(s) for Herman Fleischer

Mr. and Mrs. Chester M. Levey, Jr.

Mr. John McLean

Tribute(s) for Sam Von Lintel

Mrs. Bernard Beem

Mrs. Annie Szilagyi

Tribute(s) for Claire D. Liquorman

Mr. and Mrs. Thomas H. Perry

Mr. Kevin Bittel

Mr. and Mrs. W. Wayne Beem

Tribute(s) for Lucas S. Garbutt

Mr. and Mrs. David H. Mintz

Steps, Inc.

Tribute(s) for Kenneth Wyer

Mr. and Mrs. George J. Black

Ms. Gloria L. Garbutt

Tribute(s) for Sherril A. Malesky

Termotto & Davis Dental Practice, LLC

Ms. Michelle M. Brown

Mr. and Mrs. Carl Breitlow

Tribute(s) for Jackie Garvie

Mrs. Audrey Malesky

Mr. and Mrs. George Wallace

Mrs. Tina Calich

Mr. and Mrs. Loren Buntrock

Mrs. Eleanor Anton

Tribute(s) for Brian Mallon

Mr. and Mrs. JD Walton

Mr. and Mrs. Benjamin P. Dag

Mr. and Mrs. Gordon Buntrock

Ms. Rose Koble

Mr. and Mrs. Malachy E. Mallon

Tribute(s) for James Mulvey

Mr. and Mrs. Lawrence R. Golla

Mr. and Mrs. Paul Buntrock

Tribute(s) for Andrew J. Geljookian

Tribute(s) for Melinda J. Marten

Mr. and Mrs. John D. Fisher

Ms. Eleanor T. Keegan

Mr. Ted M. Byers

Mr. and Mrs. George P. Quinn, Jr.

Mrs. Judith Marten

Mr. and Mrs. Frances Mulvey

Mr. and Mrs. Bruce Larrabee

Mr. and Mrs. Michael D. Coleman

Tribute(s) for Eileen Gibbons

Tribute(s) for Sheila Marton

Tribute(s) for Regina Murphy

Ms. Maureen McGann

Mr. and Mrs. Myron Dagley

Mr. Daniel P. Gibbons

Mr. and Mrs. Richard Beldner

Mr. and Mrs. Frank Seiling

Mr. and Mrs. R.A. Rylowicz

Mr. and Mrs. M.E. Dahl

Tribute(s) for Jim Gibbons

Mr. Frederic Marton and Mrs. Nina

Tribute(s) for Paula J. Mutch

Mr. and Mrs. John L. Schneider

Mr. and Mrs. Dennis F. Debennette

Mr. Daniel P. Gibbons

Ms. Frances Martinson

Mr. and Mrs. Salvatore P. Terracina

Ms. Kathleen Evert

Tribute(s) for Cary Golden

Mr. and Mrs. Stuart Marton

Tribute(s) for Alexander D. Nadeau

Tribute(s) for Theodore J. Ziemba

Dr. Lynn Florian

Mr. Frank Turman

Mr. and Mrs. Peter Rapaport

Mrs. Judy Bostwick

Mr. and Mrs. Robert Cennamo

Mr. and Mrs. Steven M. Gunderson

Tribute(s) for Estelle Golden

Tribute(s) for Estelle Mauer

Tribute(s) for Michael Nardone

Mr. and Mrs. John T. Heeter

Mr. Kevin Costigan

Mr. and Mrs. Gerald Friedman

Mr. and Mrs. Anthony J. Nardone

Jim Burke Excavating, INC

Tribute(s) for James H. Graetz

Tribute(s) for Mark Mausner

Tribute(s) for Donna N. Nash

Mr. and Mrs. Richard Kuchnia

Mr. and Mrs. James F. Kurtz

Ms. Alison Baenen

Mr. and Mrs. Brad Oldenburg

Mr. and Mrs. Scott D. Lange

Tribute(s) for Dallas Greeling

Mr. and Mrs. Richard A. Barron

Tribute(s) for Richard H. Nicely

Mrs. Sandra Linna

Mr. and Mrs. Kenny Johnson

Mrs. Rebecca B. Boone

Mr. Lonnie Bates

Mr. and Mrs. Brian Lother

Tribute(s) for Todd Hartz

Dr. and Mrs. Mark Born

Mr. and Mrs. Foy L. Beeler

Mr. and Mrs. Terry R. McNabb

Mr. and Mrs. Frank Blozusky, DMD

Ms. Harolyn L. Cardozo

Mr. and Mrs. Raymond B. Coffey

Mr. and Mrs. Brian E. Melin

Mr. and Mrs. Karl R. Sassaman

Mr. and Mrs. Andrew Duffy

Johnson Chapel Free Will Baptist Church

Modern Heating Company

The Hershey Company

The Doyle Family

Mr. and Mrs. William E. McGinnis

Mt. Olivet Memorial Park, LTD

Tribute(s) for Anne Heilman

Dr. and Mrs. Douglas E. Feldman

Mr. and Mrs. William D. Mitchell

Olson Comfort Services, Inc

Dr. and Mrs. Robert Abrams

Forest Laboratories, Inc

Mr. and Mrs. Dwight O. Moberly

Mr. and Mrs. Thomas R. Rice

Mr. William D. Bell Sr.

Ms. Carol R. Ginsburg

Mrs. Karen Roper

C. Block

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Special Events

TS Alliance Announces “National” Step Forward to Cure TSC Event for Washington, DC Join us for a new “national” Step Forward to Cure TSC walk that signifies standing together and being counted as a national presence! Scheduled for June 16 on the National Mall in Washington, DC, we want to gather as many of our members and supporters as possible. This is about individuals and families gathered shoulder to shoulder and making their voice heard to Congress and to promote awareness of our cause. It also provides the opportunity for those without walks in their local community to join together for this inaugural event. Participants will step forward and be counted in the Capitol. Bring a crowd and help us make this event a sellout!

Other Event Success Stories 2011 Michigan Food and Wine Tasting held December 8, 2011 at Oak Point Country Club was a great success. The event raised more than $23,000. Attendees enjoyed a very special message from keynote speaker Dr. H. Chugani, amazing wines, beers and delicious food. The live auction and raffle were especially exciting. A big

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There are many ways you can get involved, but the obvious way is to form teams. We encourage all team leaders to find up to 10 people to help and, hopefully stand beside you, on walk day. Teams are encouraged to raise at least $1,000 each. There will be a nominal registration fee of $35 for participants not raising funds. The registration fee includes a specially designed national walk t-shirt (different than other walks) and entrance to the Regional TSC Conference on June 15. The registration fee is waived for individuals raising $100 or more. Registration opens on walk day at 10:00am. The walk begins at 11:00 am and we will have food, fun, activities and presentations the whole family can enjoy. To add to your experience, on Friday, June 15, 2012, the TS Alliance will be hosting a Regional TSC Conference. You can pre-register for the walk online or at the conclusion of the conference on Friday afternoon. The education meeting is being held at the Hyatt Regency on Capitol Hill starting at 12:45 pm with sessions running throughout the afternoon. For those of you wanting to stay at the Hyatt on Friday or Saturday, the TS Alliance has secured a room rate of $159 and a limited amount of rooms. For more information on the walk, the Regional TSC Conference, or travel plans, please

thank you goes out to event chairs Bill and Gina Oliver and the major sponsors that made it such a successful evening: Hines Park Ford, Caitlin John Private Wealth Management, WM Oliver Properties, Mrs. Mary Oliver, Mr. & Mrs. Bernard Wendt, Oak Pointe Country Club, Shawn Cotton, CSW, of Imperial Beverage, Wolverine State Brewing Company, Grand Traverse Pie Company, and Mr. & Mrs. Edward Stone.

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contact Linda Gorsuch at 800.225.6872 or [email protected].

Circle of Champions
 In 2011 we introduced the Step Forward to Cure TSC Circle of Champions program. Each individual raising $10,000 or more at one of the walks held nationwide was entered in to a drawing for a big screen TV. Congratulations to our 2011 Circle of Champions winner, Margaret Cox.  Thank you to all of those that qualified for this honor and worked so tirelessly to make a difference in the lives of those living with TSC!!   » Cindy Chernow » Margaret Cox » Allyson D’Amario » Lori Day » Reiko Donato » David Fitzmaurice » Ron Heffron » Linda Jackson » Ken Kocher » Laura Marks » Debora Moritz » Mary Jane Mudd » Amaan Panjwani » Lisa Sanders » Rob Spear » Angie Wyndham

Drs. Harry and Diane Chugani, Kathy Pawlik, Gina and Bill Oliver.

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TD W illiamson generously hosted a golf tournament and dedicated the proceeds of over $ 5 ,0 0 0 t o t h e T S Alliance. The event was held October 12, 2011 at Eagle Point Golf Club in Mont Belvieu, TX. Many thanks to the many individuals who gave their time, passion and enthusiasm to this great event!

event chair Carole Pitard, raised more than $3,000 for the Unlock the Cure campaign. This has become a huge event for the local area with sales of items ranging from household goods to furniture, jewelry and antiques.

The TS Alliance of Greater Alabama held the third annual rummage sale the weekend of September 30, 2011. This event, which is successful due to the hours and hours of work by

Event Chair Carole Pitard and daughter with community member John McBride and his daughter.

Community Alliance Leadership Positions Open

Announcing Four Regional TSC Conferences in 2012

Are you looking to be more involved with the TS Alliance and your community? Do you have a few hours per month? Do you love speaking with newly diagnosed families and marching on Capitol Hill to garner support for more research funding? Then we may have just the volunteer position for you! We are looking for volunteers to support and lead the following community alliances.

Plan now to join us at any of the four Regional TSC Conferences planned for 2012. These conferences will provide attendees with results from the June Consensus Conference; updates on the latest treatment options; basic and transitional research updates; school system IEP training; and an adults with TSC forum. Each conference will feature top TSC experts, clinicians and researchers and the opportunity to have oneon- one consultations with these experts in a nurturing and supportive environment. Be sure to watch for details and dates coming soon on our website. The Regional TSC Conferences offer great opportunities to learn the latest information about treatments in TSC, meet other families to create and build upon lifelong support and friendships,

TS Alliance of Greater Chicago TS Alliance of the Pacific Northwest TS Alliance of the Upper Midwest If you would like to learn more about the positions or get involved in other ways, please contact our Senior Manager of Community Outreach, Dee Triemer at dtriemer@ tsalliance.org.

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Dancing Star of TSC Congratulations to Elana Mae Dolan as she danced her way to the most votes in our Dancing for TSC contest.  Elana will very soon be receiving her trophy and the first place prize of a 42” flat screen television. Second place and the iPad prize were awarded to Joy Pantelis!  Her dancer was the adorable Hannah! Third place and the XBox prize went to Cindy Fowler. Her dance team was made up of Stephani, Janessa, Casey, and Abbie Fowler along with Haley and Cole Lynch. Great job! Thank you all for participating and sharing your moves with us!

and learn to advocate for yourself ansd loved ones.

The tentative schedule is: Washington, DC June 15, 2012 Hyatt Regency Washington on Capitol Hill

Houston, TX June 23, 2012 Memorial Hermann Northwest Hospital

Boston, MA September, 2012 TBD

Los Angeles, CA November 21, 2012 TBD For more information please contact Dee Triemer, Senior Manager of Community Outreach at 800-225-6872 or [email protected]

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2012 Comedy for a Cure March 25, Hollywood, California

TS Alliance Staff Contact Information All staff can be contacted by email or by calling the office toll-free phone number: (800) 2256872. Staff members are available for assistance in finding resources and/or to answer any questions you may have. Note: To email a staff

T h e 11 t h A n n u a l Comedy for a Cure® benefiting the TS Alliance will be held March 25 at Holly wood’s historic Roosevelt Hotel. This event has raised $3.25 million over the last ten years and also gained extensive visibility for TSC, proving laughter really is the best medicine! The night begins with red carpet arrivals to help garner awareness of TSC. Next is a one-hour cocktail reception and silent auction, followed by comedy performances Larry Miller and a live auction. More impor tantly, L u n d b e c k ’s V i c e President of Epilepsy Beth Lewin De an will be honored this year for her tireless advocacy in the FDA approval of a treatment for infantile spasms. The TS Alliance is also pleased to announce that actor and comedian Larry Miller will be back with us as the evening’s emcee. Our Honorary Committee this year includes an elite mix of celebrities, studio executives, political leaders, corporate executives, and medical professionals.

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member, use First Initial Last Name @tsalliance. org or [email protected]. Kari Luther Rosbeck—President & Chief Executive Officer Gail Alexander—Senior Manager of Operations Executive support and oversight of office operations Linda Gorsuch—Senior Director of Development

For event, ticket, or sponsor­ship information visit w w w.comedy foracure.org or cont ac t Linda Gorsuch at 800.225.6872.

Fundraising management and oversight Tyler Hoffman—Development Coordinator Fundraising support Dena Hook—Director of Advocacy & Education Constituent support and advocacy, community outreach and government relations Jaye Isham—Senior Director of Marketing & Communications Strategic communications and marketing, media relations and online strategy oversight Jo Anne Nakagawa—Director of Clinical Projects Development and implementation of the TSC Clinical Database Project and TSC clinics liaison Mary Jane Perraut—Controller Financial management and accounting Steven L. Roberds, Ph.D.—Chief Scientific Officer Scientific affairs and medical outreach Katie Smith—Senior Associate, Science & Government Affairs Science and medical administrative support and government advocacy Dee Triemer—Community Outreach Manager Volunteer management and support

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801 Roeder Road, Suite 750 Silver Spring, MD 20910

Don’t

Forget! May is National Tuberous Sclerosis Complex Awareness Month!

And May 15 is the Inaugural TSC Global Awareness Day! Be sure to promote these on your Facebook pages and with your family, friends and co-workers!