2010 Henry Paulson Associate Research Director, NAF Review Research Ataxia

In honor of Harry Orr… University of Minnesota basketball score in the NCAA tournament? On the other hand, Michigan: Michigan 75, Tennessee 45

Funded Research for FY 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

Funded for FY Grants from three countries: – 3 Portugal – 1 United Kingdom – 6 United States

Funded for FY 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

Disease LocusGeneMutation 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 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 (not reported) Unknown CAG expansion Unknown Non-repeat mutations CAG expansion CAG expansion CTG expansion ATTCT expansion Non-repeat mutations CAG expansion Non-repeat mutations deletions CAG expansion Unknown Genomic duplication Unknown Unkknown Dominant ataxias: ~30 and still counting!

Funded for FY 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

Also Funded in 2010 Additional Research Projects: – National Ataxia Registry – Tissue Donation Program

Growth in ataxia publications in past 30 years

Modest growth in ataxia clinical trial publications in past 30 years

New 2011 Awards New Initiatives for Clinical Research on Ataxia, S.H. Subramony, MD New Initiatives for Clinical Research on Ataxia, S.H. Subramony, MD Assessment of riluzole treatment as a therapy for SCA3, Jana Boy, PhD 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 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 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 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 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 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 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 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

NAF Research Funding Amounts NAF distributed for ataxia research - – in $747,185 – In $860,208 – In $578,000 – In 2011 – Commitments for $336,000

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 : Vikram Shakkottai, MD, PhD, Univ. Michigan – Current: Guangbin Xia, MD, PhD, University of Florida Rare Disease Patient Contact Registry

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)

THANKS!!