School of Medicine to lead $6.25 million NIH research program on common inherite

[Guest guest]

School of Medicine to lead $6.25 million NIH research program on common

inherited neurological disorder

http://prognosis.med.wayne.edu/

The National Institutes of Health announced yesterday a second phase of the Rare

Diseases Clinical Research Network totaling $117 million, which includes funds

for 19 research consortia. Wayne State University received a five-year, $6.25

million research grant from the National Institute of Neurological Disorders and

Stroke. The grant funds an international project aimed at developing a better

understanding of and new treatments for the various forms of Charcot-Marie-Tooth

disease.

Charcot-Marie-Tooth disease is one of the most common genetic nerve diseases,

affecting one in 2,500 people, or 120,000 Americans. CMT causes progressive

muscle weakness, painful foot deformities and walking difficulty. As the disease

progresses, weakness and muscle atrophy occur in the hands, resulting in

difficulty with fine motor skills. Symptoms vary, with pain ranging from mild to

severe. Some patients rely on foot or leg braces or other orthopedic devices to

maintain mobility. To date, no effective therapies are available for any form of

CMT.

Shy, M.D., professor of the Department of Neurology for the School of

Medicine, leads the study, which aims to provide insights into disease

mechanisms, develop therapies and educate future research of inherited

neuropathies such as CMT.

Dr. Shy said there are mutations in more than 40 different genes causing CMT in

millions of patients. " Modern genetics and cell biology make developing

treatments for these disorders a realistic possibility, " Shy said. " However,

many of the individual forms of CMT are rare, so to better understand the

different forms of CMT and develop rational treatments for them requires

national and international collaborations between neurologists and scientists. "

The project has specific goals geared toward establishing a Rare Disease

Clinical Research Center for inherited neuropathies. In particular, the group

will determine the natural history of the most common forms of CMT that lack

this information.

" At Wayne State, we have pioneered the natural history studies for the two most

common forms of CMT -- CMT1A and CMTX, " Dr. Shy said. " Our results are used by

neurologists around the world to design clinical trials for these disorders.

However, for the types of CMT to be studied in this project, we do not see

enough patients at WSU to perform natural history studies by ourselves, hence

the critical nature of having a national and international collaboration. "

In addition, the project aims to identify " modifier genes " in CMT1A, the most

common inherited neuropathy. CMT1A affects about half of all patients with CMT

and is caused by an identical genetic mutation in all patients. In collaboration

with the Human Genomic Institute at the University of Miami, the group will use

21st century gene sequencing techniques to identify these modifier genes to

determine how severely patients will be affected. Using the same techniques,

University of Miami researchers will identify the genetic cause of CMT in

families in which only a few members have been affected, something previously

not possible.

The project also will study children affected by CMT. The consortium will

develop a pediatric scoring system that will be used worldwide to measure

impairment and progression of disability in children with CMT. The collaborators

also will establish a new Web site to provide patients, their families and

scientists around the world with the latest CMT information. The consortium also

will provide international training for clinical and research doctors to train

the next generation of researchers of CMT and other neurodegenerative diseases.

Wayne State University has one of the largest and most comprehensive CMT

programs in the world. The program is translational, combining patient care and

patient clinical research with animal and cellular models of CMT. Since 1996,

WSU has evaluated more than 1,200 patients with CMT from more than 21 countries,

five continents and 46 states.

" This international project establishes Wayne State University's Department of

Neurology as the leading inherited neuropathy program in the U.S. and around the

world, " said Dr. k, chairman of Neurology for the School of Medicine.

" Under Dr. Shy's leadership, this consortium will bring us much closer to the

development of effective treatments for the various forms of CMT. "

Project collaborators include Gyula Acsadi, M.D., Ph.D., associate professor of

Neurology at WSU and director of the Pediatric MDA Clinic and Pediatric

Neurology Clinical Division chief at Children's Hospital of Michigan; Steve

Scherer, M.D., Ph.D., , professor of Neurology and vice chairman

for research in neurology at the University of Pennsylvania; M. Reilly,

M.D., director of the neuropathy clinic at the National Hospital for neurology

and neurosurgery in London, England, and head of the Peripheral Neuropathy

component of the MRC Centre for Neuromuscular Diseases at Newcastle University

and the National Hospital for Neurology and Neurosurgery; Francesco Muntoni,

M.D., professor and consultant in pediatric neurology for the Dubowitz

Neuromuscular Centre at the University College of London Institute of Child

Health; Stephan Zuchner, M.D., associate professor of medicine, Miami Institute

of Human Genomics, University of Miami; Jeffery Vance, M.D., professor of

medicine and director of the division of human genomics, University of Miami;

and Herrmann, M.D., associate professor of neurology and pathology, School

of Medicine, University of Rochester.