Common Inherited Neurological Disorders: Charcot-Marie-Tooth Disease
announced yesterday a second phase of the Rare Diseases Clinical Research
Network totaling $117 million which includes funds for 19 research consortia.
grant from the National Institute of Neurological Disorders and Stroke under
this program. The grant, "Inherited Neuropathies Consortium," is 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 (CMT) is one of the most common genetic nerve
diseases, affecting 1 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 from patient to
patient, with pain ranging from mild to severe, with some patients relying on
foot or leg braces or other orthopedic devices to maintain mobility. To date,
no effective therapies are available for any form of CMT.
To address this issue, Dr. Michael Shy, M.D., professor of neurology in the
study which aims to provide insights into disease mechanisms, develop
therapies and educate future research on inherited neuropathies such as CMT.
According to Shy, there are mutations in more than 40 different genes causing
CMT in millions of patients throughout the world. "Modern genetics and cell
biology make developing treatments for these disorders a realistic
possibility," said Shy. "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
particular, the group will determine the natural history of the most common
forms of CMT that currently lack this information. "At
pioneered the natural history studies for the two most common forms of CMT -
CMT1A and CMTX," said Shy. "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 comprises about half of all the patients
with CMT and is caused by an identical genetic mutation in all patients. In
collaboration with the Human Genomic Institute at the
group will use 21st century gene sequencing techniques to identify these
modifier genes that will help determine how severely patients will be
affected. Using the same techniques, the
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 around the world to
measure impairment and progression of disability in children with CMT. The
collaborators also will establish a new CMT Web site to provide patients,
their families and scientists around the world with the latest CMT
information. In addition, the consortium will carry out an international
training program for clinical and research doctors to train the next
generation of researchers for CMT and other neurodegenerative diseases.
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 in addition to
coming from the National Institutes of Health, Muscular Dystrophy Association
and Charcot-Marie-Tooth Association.
Along with Shy, 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
and vice chair for research in neurology at the
Mary M. Reilly, M.D., director of the neuropathy clinic at the National
Hospital for neurology and neurosurgery in
Peripheral Neuropathy component of the MRC Centre for Neuromuscular Diseases
at
Neurosurgery; Francesco Muntoni, M.D., professor and consultant in paediatric
neurology in the Dubowitz Neuromuscular Centre at the
London Institute of Child Health; Stephan Zuchner, M.D., associate professor
of medicine, Miami Institute of Human Genomics,
Vance, M.D., professor of medicine and director of the division of human
genomics,
of neurology and pathology,
"This international project establishes
Neurology as the leading inherited neuropathy program in the
the world," said Dr. Robert Lisak, chair of neurology in 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."
universities in an urban setting. Through its multidisciplinary approach to
research and education, and its ongoing collaboration with government,
industry and other institutions, the university seeks to enhance economic
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