Another piece of the puzzle

The DMRF is committed to advancing research and achieving our mission of identifying new and more effective treatments and ultimately a cure for all forms of dystonia. The Foundation has proudly supported most of the world’s leading dystonia researchers resulting in discovery of pieces of the dystonia puzzle. This past week, our understanding was again advanced with the publication of a study that was supported by the DMRF and the National Institute of Neurological Disorders & Stroke.

DMRF grant recipient Flavia Nery, PhD and longtime dystonia investigator Xandra Breakefield, PhD 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. 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, PhD 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.

Why not?

For nearly 35 years, the DMRF has been asking questions of our researchers, pushing them for scientific answers and always moving forward with a “can-do” attitude. At first, it was an uphill battle – trying to convince researchers that this was a field worthy of their time and energy. Recently, we have seen more activity and enthusiasm around dystonia research, more information and more progress. This is all to be celebrated by everyone in the dystonia community! We want you to know that the DMRF continues to push – asking ourselves, “Why not?” Why shouldn’t we take what we now know and push the science further to see what we learn? This is why the Foundation is taking the next step with a major project that we hope will lead to identifying proteins that modify the DYT1 dystonia phenotype. The concept is to use a genetic approach based on silencing selected genes and monitoring the effect of such silencing on torsinA function. This is a high-risk project, but the Foundation feels strongly that it needs to be done as it may possibly lead to potential drug targets and, eventually, to new treatments. Our Science Officer, Dr. Jan Teller, will manage this pioneering new project. This phase of the project began this week, and will continue through the Spring of 2011. We are very excited about this work. Look for a formal announcement in the next week, but we wanted to let you know early about this one way in which the spirit that founded DMRF – pushing for action and answers -- continues today.