Gene Linked to Epilepsy, Movement Disorder Identified, Cleveland Clinic-Led Research

Main Category: Epilepsy
Article Date: 06 Jun 2005 - 10:00 PDT

email to a friend   printer friendly   opinions  

Researchers led by scientists at The Cleveland Clinic have identified the first gene in patients who have epilepsy associated with a movement disorder called paroxysmal dyskinesia. The study provides the first direct genetic evidence that the co-existence of these conditions represents a new syndrome.

Future research will seek to use the discovery to identify and develop new treatments for the neurological conditions. Complete research findings will appear June 5 in the online version of Nature Genetics and in the July print edition.

"Epilepsy and movement disorders like paroxysmal dyskinesia (PD) are distinct diseases, but increasingly they are found to affect the same patient or the same family," said Qing Wang, Ph.D., one of the study's lead investigators and director of the Center for Cardiovascular Genetics and the Department of Molecular Cardiology at The Cleveland Clinic's Lerner Research Institute. "The study is significant clinically because it raises awareness of coexistent epilepsy and PD as a distinct clinical entity."

Epilepsy is a common and debilitating neurological disorder affecting more than 40 million people worldwide. It is caused by disruptions in the electrical signals of the brain, resulting in seizures. Paroxysmal dyskinesia also is a neurological disorder. It is characterized by sudden, unpredictable, disabling attacks of involuntary movement. Typically, PD attacks do not result in a loss of consciousness, which often occurs with epilepsy.

"This paper provides insight into the development of epilepsy and paroxysmal movement disorders and has important implications for future research into these disorders," said Jocelyn F. Bautista, M.D., the study's other lead investigator and associate staff physician in the Department of Neurology, Section of Epilepsy, at The Cleveland Clinic.

The new research is based on the genetic analysis of a large, multi- generational family of mixed European descent. Sixteen family members were known to have epilepsy, PD or both conditions; four had epilepsy only; seven had PD only, and five suffered from both conditions.

By examining genetic markers and landmarks on human chromosomes 1 to 22, researchers identified a mutation in an ion channel gene, KCNMA1 (making the BK potassium channel), that causes epilepsy and PD. The mutation was found only in the 16 family members diagnosed with these conditions. In turn, of the more than 500 healthy individuals used as a control population in the study, none carried the mutation.

The finding could serve as the basis for the development of new therapies and medications for patients with epilepsy and PD.

"We believe that there is a strong likelihood that this discovery will yield important new products," said Christopher Coburn, executive director of CCF Innovations, the Clinic's technology transfer and commercialization arm. "We look forward to engaging companies seeking to develop diagnostic and therapeutic neurological products and have filed patent protection to enable that exchange," he said.

"Ion channels are attractive targets for drug development because they are proteins on the surface of cells," Dr. Wang said. "We found that patients in our study have a hyperactive KCNMA1 gene. This means that a pharmaceutical agent that blocks the BK potassium channel may be effective in preventing epilepsy and PD in these patients."

In addition to Drs. Wang and Bautista, other Cleveland Clinic researchers involved in the research included Wei Du, M.S., co-lead author on the paper, Sun-Ah You, Ph.D.; Lejin Wang, M.D.; Prakash Kotagal, M.D., and Hans O. Luders, M.D., Ph.D., chairman of the Department of Neurology at the Clinic. Jianmin Cui, Ph.D., and his colleagues at Washington University in St. Louis and George Richerson, M.D., Ph.D., and his colleagues at Yale University also were involved in the research.

The Lerner Research Institute is home to all laboratory-based research at The Cleveland Clinic Foundation. Its mission is to understand the causes of human diseases and to develop new treatments and cures. The Lerner Research Institute is ranked fifth in NIH funding among all U.S. research institutes in 2004. More than 1,100 people work in research programs focusing on cardiovascular, cancer, neurologic, musculoskeletal, allergic and immunologic, eye, metabolic, and infectious disease. The Institute also is an integral part of the new Cleveland Clinic Lerner College of Medicine of Case Western Reserve University - training the next generation of physician-scientists and the first medical school to be accredited in 26 years.

The Cleveland Clinic Foundation, located in Cleveland, Ohio, is a not-for- profit multispecialty academic medical center that integrates clinical and hospital care with research and education. The Cleveland Clinic was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. U.S. News & World Report consistently names The Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. Approximately 1,500 full-time salaried physicians at The Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2004, patients came for treatment from every state and 100 countries. The Cleveland Clinic website address is http://www.clevelandclinic.org.

The Cleveland Clinic Foundation
http://www.clevelandclinic.org

• Additional
• References
• Citations