2010

Henry PaulsonAssociate 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 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

Funded for FY 2010

10 Grants from three countries:– 3 Portugal– 1 United Kingdom– 6 United States

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

Disease Locus Gene Mutation

SCA 1SCA 2SCA3 (MJD)SCA 4SCA 5SCA 6SCA 7SCA 8SCA 10SCA 11SCA 12SCA 13SCA 14SCA 15/16SCA 17SCA 18SCA 19SCA20SCA 21SCA 22SCA 23….

6p12q14q116q11p19p3p13q22q15q5q19q19q3p6q7q1p117p1p20p

Ataxin 1Ataxin 2Ataxin 3UnknownB III SpectrinCACNA 1Ataxin 7SCA8SCA10 TTBK2/kinase  PPP2R2B KCNC3PKRCGITPR (IP3)TBPUnknownUnknown(not reported)UnknownUnknownUnknown

CAG expansionCAG expansionCAG expansionUnknownNon-repeat mutations CAG expansionCAG expansionCTG expansionATTCT expansionNon-repeat mutationsCAG expansionNon-repeat mutationsNon-repeat mutationsdeletionsCAG expansionUnknownUnknownGenomic duplicationUnknownUnknownUnkknown

Dominant ataxias: ~30 and still counting!

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

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 • 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

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

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!!