2010
Ataxia
Research Review
Henry Paulson
Associate Research Director, NAF
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
Dominant ataxias: ~30 and still counting!
Disease
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….
Locus
6p
12q
14q1
16q
11p
19p
3p
13q
22q
15q
5q
19q
19q
3p
6q
7q
1p
11
7p
1p
20p
Gene
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
Mutation
CAG expansion
CAG expansion
CAG expansion
Unknown
Non-repeat mutations
CAG 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
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
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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 ataxin3, 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 noninvasive 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!!