2010

1. Ataxia Research Review 2010 Henry Paulson Associate Research Director, NAF

2. In honor of Harry Orr… University of Minnesota basketball score in the NCAA tournament? On the other hand, Michigan: Michigan 75, Tennessee45

3. Funded Research for FY 2010 • 10 Grants for: • 3 Young Investigator Awards • 2 Fellowship (Post-Doc) Grants • 5 Research Grants (seed-money) High priority: promote the next generation of ataxia researchers

4. Funded for FY 2010 10 Grants from three countries: • 3 Portugal • 1 United Kingdom • 6 United States

5. Funded for FY 2010 • 10 grants in research on: • 4 Projects in SCA3 • 1 Project each in SCAs 5,6,7 • 1 Project in AOA2 • 1 Project : Biomarkers in SCAs & MSA-C • 1 Project: Genetic modifiers in SCAs MANY causes of ataxia, both genetic and nongenetic

6. Disease Locus Gene Mutation SCA 1 SCA 2 SCA3 (MJD) SCA 4 SCA 5 SCA 6 SCA 7 SCA 8 SCA 10 SCA 11 SCA 12 SCA 13 SCA 14 SCA 15/16 SCA 17 SCA 18 SCA 19 SCA20 SCA 21 SCA 22 SCA 23…. 6p 12q 14q1 16q 11p 19p 3p 13q 22q 15q 5q 19q 19q 3p 6q 7q 1p 11 7p 1p 20p Ataxin 1 Ataxin 2 Ataxin 3 Unknown B III Spectrin CACNA 1 Ataxin 7 SCA8 SCA10  TTBK2/kinase PPP2R2B KCNC3 PKRCG ITPR (IP3) TBP Unknown Unknown (not reported) Unknown Unknown Unknown CAG expansion CAG expansion CAG expansion Unknown Non-repeat mutationsCAG expansion CAG expansion CTG expansion ATTCT expansion Non-repeat mutations CAG expansion Non-repeat mutations Non-repeat mutations deletions CAG expansion Unknown Unknown Genomic duplication Unknown Unknown Unkknown Dominant ataxias: ~30 and still counting!

7. Funded for FY 2010 • 10 grants in research on: • 4 Projects in SCA3 • 1 Project each in SCAs 5,6,7 • 1 Project in AOA2 • 1 Project : Biomarkers in SCAs & MSA-C • 1 Project: Genetic modifiers in SCAs MANY causes of ataxia, both genetic and nongenetic

8. Also Funded in 2010 Additional Research Projects: • National Ataxia Registry • Tissue Donation Program

9. Growth in ataxia publications in past 30 years

10. Modest growth in ataxia clinical trial publications in past 30 years

12. New 2011 Awards • New Initiatives for Clinical Research on Ataxia, S.H. Subramony, MD • Assessment of riluzole treatment as a therapy for SCA3, Jana Boy, PhD • Developing an SCA3 therapeutic: small molecules that reduce levels of mutant ataxin-3, Maria do Carmo Pereira da Costa, PhD • Determination of secondary structure of Ataxin-3 by X-ray crystallography, Mee Whi Kim, PhD • Inhibition of ataxin-1 phosphorylation: screening potential therapeutics of SCA1., Sarita Lagalwar, PhD • Nuclear events affected by Ataxin-1, Chih-Cheng Tsai, Ph.D. • Disclosing the mitochondrial connection to Purkinje dark cell degeneration in the SCA28 mouse model, Giorgio Casari, PhD • Evaluation of lead compounds that prevent frataxin degradation in a Friedreich's ataxia mouse model, Roberto Testi, MD • Generation of an improved humanized mouse model of FRDA containing a long GAA trinucleotide repeat expansion, Joseph P. Sarsero, PhD • Magnetic Resonance Imaging and Spectroscopy of the brain in patients with Friedreich's Ataxia and Ataxia with Oculomotor Ataxia type 2: searching for non-invasive biomarkers, Isabelle Iltis, PhD

14. NAF Research Funding Amounts • NAF distributed for ataxia research - • in 2008 - $747,185 • In 2009 - $860,208 • In 2010 - $578,000 • In 2011 – Commitments for $336,000

15. CRC-SCA NIH funded Rare Disease Clinical Research Consortium • 11 Research Sites • Natural History Study • Genetic Modifiers • NAF FAQs available explaining this study • Trainee • Former : VikramShakkottai, MD, PhD, Univ. Michigan • Current: Guangbin Xia, MD, PhD, University of Florida • Rare Disease Patient Contact Registry

16. Another NIH funded Rare Disease Clinical Research Consortium:CINCH(Clinical Investigation of Neurologic Channelopathies) Episodic Ataxias – Dr. Joanna Jen (some progressive forms of ataxia also are caused by channel defects)

17. THANKS!!