Clinical Research Network for Spinocerebellar Ataxias

By Tetsuo Ashizawa, MD
Department of Neurology
University of Florida

April/May 2010

One day in September 2009 I was in an NIH Study Section meeting in Bethesda, and my cell phone rang. It was Dr. Wendy Galpern of NINDS calling. She told me incredible news - NINDS would fund our RC1 "Challenge Grant" application to establish the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA), and I need to prepare the necessary documents in two weeks. She also told me that, thanks to Dr. Dan Tagle of NINDS and Dr. Steve Groft of Office of Rare Disease Research (ORDR), the CRC-SCA might be able to join the NIH Rare Disease Clinical Research Network (RDCRN). I could not help raising my voice with joy and excitement. Dr. Galpern still teases me about my elated response, with which she could imagine I was almost like dancing with her on the phone.

Spinocerebellar ataxias are heterogeneous disorders. The majority of the dominantly inherited ataxias are named with prefix SCA followed by a number in the order of the discovery of the locus. The latest SCA is SCA32 and the number is expected to increase. Various mutations have been identified in about one half of them, and expanded CAG repeats, especially those encoding polyglutamine expansions, are the most common mutations. Pathogenic mechanisms of many SCAs are increasingly becoming clear, and therapeutic strategies based on understanding the disease mechanism are being developed. Many advances have been reported and discussed in the translational context at the 3rd Ataxia Investigators Meeting (AIM) organized by National Ataxia Foundation (NAF) held in Chicago from March 9 to 11, 2010. The ataxia communities, both patients and researchers, are excited about these advances and expect increasing activities of clinical trials in coming years.

The clinical trial infrastructures are badly needed for SCAs. There have been concerted efforts for Friedreich's ataxia (FA), the most common autosomal recessive ataxia, whose disease mechanism is now known as a loss of function of frataxin. Clinical trials are ongoing for several drugs for FA in US and Europe. For SCAs, the Cooperative Ataxia Group (CAG), which was formed in late 1990's attempted to organize SCA clinical trial infrastructures in US. NAF has provided funding to CAG investigators to initiate a natural history database at UCLA and a patient registry at Emory University.

However, the major effort was not launched until European investigators obtained funding from the European Union (EU) to establish the EuroSCA in 2004. EuroSCA capitalized this opportunity to collect data on the natural history of SCAs and established the SCA registries. Unfortunately, EU recently decided not to continue this funding despite the EuroSCA's monumental success. In 2009, the grant programs supported by the American Recovery & Reinvestment Act (ARRA) were launched to support job-creating research in US. The RC1 funding that the CRC-SCA is receiving is one of the ARRA grants, and will be used to expand the effort started by EuroSCA.

The RC1 grant mechanism turned out to be highly competitive; only 880 of 20,000 applications were funded. After learning about disappointments of many of my colleagues who received apparently excellent scores for their RC1 applications without funding, I emailed my co-investigators telling "thanks for your cooperation but don't get your hopes up." So, Dr. Galpern's call on the RC1 funding was truly surprising to me. It provides a total cost of $1 million over two years (i.e., $500,000 per year for two years).

Our Specific Aims are to (1) establish the CRC-SCA, (2) recruit SCA patients and obtain longitudinal clinical data for future clinical trials, (3) initiate a pilot study to determine genetic modifiers of SCA, and (4) train physician-scientist investigators for clinical and translational research of SCA. The CRC-SCA will focus on SCAs 1, 2, 3 and 6, which are among the most common SCAs, although the patient registry will accept subjects with any types of ataxia.

Participating centers include Emory University, Harvard University, Johns Hopkins University, University of Chicago, UCLA, University of Florida, University of Michigan, University of Minnesota, University of South Florida and University of Utah. We are also expecting collaborations with Federal University of Paraná, Brazil and the Ataxia Study Group (the successor of EuroSCA). The CRC-SCA has been fully incorporated into the RDCRN, and the Data Management Coordination Center (DMCC) of the RDCRN will deposit our data and make the data publically accessible. We are completing the multicenter IRB approval process, and should be able to initiate the study soon.


About Dr. Tetsuo Ashizawa

Tetsuo Ashizawa, MD, FAANDr. Tetsuo Ashizawa is Professor and Chairman of the Department of Neurology at the University of Florida, Gainesville, Florida. Dr. Ashizawa also holds the Melvin Greer Professor of Neurology. Dr. Ashizawa received his medical degree from the Keio University School of Medicine in Tokyo in 1973. He completed his neurology residency training and subsequent clinical and basic science fellowships at Baylor College of Medicine. In 1981 he joined the faculty at Baylor, where he climbed to the academic rank of tenured Professor 1997. In 2002 Dr. Ashizawa was recruited to the University of Texas Medical Branch (UTMB) in Galveston, Texas to chair the Neurology Department, and then moved to Gainesville, Florida in April 2009 as Chair of the Department of Neurology at UF. He has published over 180 papers in leading scientific and clinical journals and Books.

Dr. Ashizawa's basic science research projects have primarily been focusing on neurogenetic disorders caused by expanded short tandem repeats, including myotonic dystrophy, Friedreich's ataxia and autosomal dominant spinocerebellar ataxias. His current research is to investigate the pathogenic mechanism of spinocerebellar ataxia type 10 (SCA10). Dr. Ashizawa is also the principal investigator of a nationwide consortium for clinical research on SCA1, SCA2, SCA3 and SCA6. This consortium is one of the Rare Disease Clinical Research Consortia (RDCRC) organized and funded by the National Institute of Health (NIH). This consortium will establish the infrastructure and database to prepare for future clinical trials of new therapies for SCAs.

For more information, contact:

Tetsuo Ashizawa, MD, FAAN
Melvin Greer Professor
Department of Neurology
University of Florida
100 South Newell Drive
L3-100, PO Box 100236
Gainesville, FL 32611
Phone (352)273-5550
Fax (352)273-5575


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