Study Published in Major Journal
CHICAGO, July 20, 2011 /PRNewswire-USNewswire/ -- Dystonia Medical Research Foundation (DMRF) grant recipient Flavia Nery, Ph.D. and longtime dystonia investigator Xandra Breakefield, Ph.D. of Harvard‘s Massachusetts General Hospital, and their collaborators have discovered a significant clue toward understanding why a mutation in the DYT1 gene might lead to dystonia, a debilitating neurological disease.
It was in Dr. Breakefield’s lab at Harvard where the DYT1 gene and the protein it encodes, torsinA, were discovered more than 10 years ago. TorsinA function has since been a mystery. Scientists have been working for years to make the connection between this mutated protein and the electrical signals in the brain that lead to the uncontrollable muscle contractions and spasms that are characteristic of dystonia.
According to the paper published in the prestigious online journal, Nature Communications, torsinA is involved in eliminating misfolded proteins from a part of the cell called the endoplasmic reticulum. When mutant torsinA, which causes DYT1 dystonia, is present, it interferes with this process, making cells unusually vulnerable to cellular stress that may compromise neuronal function. This work demonstrates a cellular link between the disease-causing torsinA mutation and fundamental mechanisms of neuronal dysfunction that may ultimately lead to dystonia.
DMRF Science Officer Jan Teller, MA, Ph.D. explains, “Essentially, all dystonia disorders are considered a neural circuits malfunction. Therefore finding any molecular or biochemical way to put these circuits back ‘in order’ would be beneficial to all dystonias. Understanding how this works in DYT1 dystonia may suddenly open up new possibilities for designing dystonia-specific treatments.” Current dystonia therapies such as botulinum neurotoxin injections and deep brain stimulation surgery suppress symptoms without altering or improving the course of the disease. A new generation of therapies that target dystonia at the cellular level would be revolutionary to the field and could provide relief to thousands of patients.
The paper is entitled, “TorsinA participates in endoplasmic reticulum-associated degradation.” Authors: Flavia C. Nery, Ioanna A. Armata, Jonathan E. Farley, Jin A. Cho, Uzma Yaqub, Pan Chen, Cintia Carla da Hora, Qiuyan Wang, Mitsuo Tagaya, Christine Klein, Bakhos Tannous, Kim A. Caldwell, Guy A. Caldwell, Wayne I. Lencer, Yihong Ye, Xandra O. Breakefield. The abstract can be viewed at http://www.nature.com/ncomms/journal/v2/n7/full/ncomms1383.html.
The study was supported by the National Institute of Neurological Disorders & Stroke and by the Dystonia Medical Research Foundation.
Dystonia is a neurological movement disorder that causes muscles to contract and spasm involuntarily. The involuntary muscle contractions force the body into repetitive and often twisting movements as well as awkward, irregular postures. Dystonia affects men, women, and children of all ages and backgrounds. Estimates suggest that no less than 300,000 people in North America are affected. Dystonia causes varying degrees of disability and pain, from mild to severe.
Founded in 1976, the Dystonia Medical Research Foundation (DMRF) is a 501(c)3 organization dedicated to serving all people impacted by dystonia. The mission is to advance research, promote awareness and education, and support the well-being of affected individuals and families. More information may be obtained by contacting the Dystonia Medical Research Foundation at 312-755-0198 or visiting www.dystonia-foundation.org.
Contact: Janet Hieshetter, Executive Director
Dystonia Medical Research Foundation
Ph: 312-755-0198 E: jhieshetter@dystonia-foundation.org
SOURCE Dystonia Medical Research Foundation
