NATIONAL ATAXIA REGISTRY AND NATURAL HISTORY STUDY

1. S H Subramony M.D. Professor of Neurology McKnight Brain Institute and University of Florida College of Medicine Gainesville, FL NATIONAL ATAXIA REGISTRY AND NATURAL HISTORY STUDY

2. DISEASE REGISTRIES • Special database containing information about persons with specific diseases • Data is systematically collected and standardized • Data entry • Patients • Physicians and health care providers • Researchers • EMR’s • Usefulness • Promote research • Easier patient recruitment for studies and trials • Genotype/phenotype information • Link repositories and other data resources • Therapy effectiveness • Knowledge dissemination

3. NATIONAL ATAXIA REGISTRY • Database that collects basic information on patients with “degenerative” ataxia • “Contact” registry: contact information and diagnosis • “Curated”: we confirm the diagnosis as much as possible • What type of patients can participate? • Patients with ataxia not caused by an obvious and known disease like MS, strokes, tumors, infections etc • Patients with inherited and sporadic ataxias of all types • You don’t have to need a definite diagnosis of cause, only that you have ataxia

4. PURPOSE OF NAR • Facilitate clinical research including drug trials in the field of ataxias • Bring appropriate research groups in touch with the right group of patients • Caveats • Registry participation does not guarantee participation in a drug trial • You do not commit to participation in any trial or study

5. ELIGIBLE SUBJECTS • Inherited ataxias • Dominant (SCA 1,2,3,5,6,7,8,10,12,13,14,17,DRPLA, other uncertain types) • Recessive (FA, AOA, POLG/MIRAS, AT, other types) • Mitochondrial, X-linked including FXTAS • Sporadic ataxia (MSA, OPCA, idiopathic ataxia) • Congenital ataxia • Any other degenerative ataxias including gluten ataxia, GAD ataxia • Subjects at risk for inherited ataxias(usually dominant) • All inclusive

6. REGISTRY PROCESS • Visit the web site (directly or through the NAF web site) www.nationalataxiaregistry.org • Click on new user log in on home page • Enter essential contact information on page 2 • Enter and confirm e mail address, choose a password and a security question on page 3 • Print informed consent from page 4 • Coordinator will contact you for telephonic consent before activating the account • Once activated you will be able to log back and enter diagnostic details and basic information on “functional stage” KEEP PASSWORD WRITTEN IN SECURE PLACE SEND COPY OF KEY DIAGNOSTIC DOCUMENT WITH CONSENT

9. NAR 2012 • 1154 subjects have provided initial contact information • 343 subjects have completed consent and submitted diagnostic information

10. NUMBER OF SUBJECTS WITH DIFFERENT DIAGNOSES

11. Gender ratios Current age

12. Age at onset Functional stage

13. OBSTACLES AND COMING CHANGES • Two step process, IRB mandated • Need for telephonic consent with each individual, return of singed paper consent • Volunteer soft ware consultants • E mail username • Multiple diagnoses • New ongoing initiatives • Back up compensated consultant • Negotiation with UF IRB for approving web based consent • Other necessary amendments to the protocol

15. THE CLINICAL RESEARCH CONSORTIUM FOR SPINOCEREBELLAR ATAXIA • The CRC-SCA includes all the centers participating in the NIH funded natural history study of SCA 1,2,3 and 6 and all are members of the CAG • The aim of this study is to collect information on US patients with SCA 1,2,3, and 6 regarding the natural progression of the disease, identify the best methods to assess disease progression and find any genetic markers that may influence the characteristics of the disease

16. PARTICIPATING SITES

17. NATURAL HISTORY DATABASE • Natural History Database is important for understanding the disease progression, which will be critical in designing most clinical trials. • Only individuals with the diagnosis of SCA1, 2, 3 and 6 are included in the Natural History Database. • Visits occur every 6 month. • Each visit involves an interview, a physical examination, timed-measurement such as 25 meter (8 ft) walk and 9-hole peg board testing. • The first/baseline visit is used to consent the patient • Blood is drawn once and tested for DNA modifiers at University of Utah lab. • A subset of patients will undergo home-based ataxia testing (gait monitor and computer on-line click test).

19. Ataxia patients SCA1,2,3&6 RDCRN Website CRC-SCA Investigators National Ataxia Registry Clinical data collection Blood samples DMCC Natural History Database NAF/UCLA Natural History Database Utah Genetic Modifier Database DMCC Genetic Modifier Database

20. NATURAL HISTORY STUDY Columns 1-6: American Indian, Asian, Pacific Islander, African American, White and other

21. AGE AT REGISTRATION AND DURATION OF DISEASE

22. NUMBER OF SUBECTS AND MEAN AGE AT ONSET Mean age at onset Number of subjects

23. MEAN SCORES AT BASELINE VISIT SARA, walk test, peg board test Functional stage

25. SAMPLE SIZE ESTIMATES • Number needed per arm to detect 50% reduction in disease progression in 1 year: 143 for 9HPT, 250 for SARA and 275 for SCAFI

26. SUMMARY • NAR has continued to accrue subjects • Substantial number of subjects have no definite causative diagnosis • Issue of informed consent is a difficult one • CRC-SCA • Has generated substantial natural history data • Sample size estimates still disappointingly large • International collaboration may be needed and is being initiated

27. AKNOWLEDGEMENTS • Becca Beaulieu • Tommy Zhu • Sue Hagen • Bill Hartnett • Marty Ohmann • Tee Ashizawa • CRC- consortium investigators