21 Oct Bipolar Disorder: Protective Genetic Discovery May Lead To New Drug Treatment
MedicalResearch.com: Interview with:
Edward I. Ginns, MD, PhD, Director
Program in Medical Genetics and
Lysosomal Disorders Treatment and Research Program
University of Massachusetts Medical School
Reed Rose Gordon Building, Room 137
Shrewsbury, MA 01545
Medical Research: What are the main findings of the study?
Dr. Ginns: Our study identified that sonic hedgehog signaling, an important brain pathway, is involved in bipolar affective disorder.
This finding shows a mechanism and provides new targets for drug development. It suggests that sonic hedgehog signaling can be modulated to help manage bipolar symptoms in adults by using drugs already being studied in clinical trials for other medical conditions.
The new findings were uncovered by decades of translational research in the Old Order Amish families of Pennsylvania, where in a few special families in the Amish Study there is a high incidence of both bipolar disorder and a rare genetic dwarfism, Ellis van‐Creveld (EvC) syndrome. No person with EvC had bipolar disorder despite forty years of documented research across multiple generations, suggesting that the genetic cause of this rare dwarfism was protective of bipolar affective disorder.
Medical Research: What was most surprising about the results?
Dr. Ginns: We connected bipolar disorder to the sonic hedgehog pathway that is known to be important to brain function and that contains druggable targets.
Our discovery was essential to integrating pieces of the molecular puzzle. The overriding protective effect of the genetic mutation in Ellis van‐Creveld syndrome in the Amish led us to an important brain signaling pathway with potential novel targets for drug development for bipolar disorder. Our study went beyond finding associations with risk genes. Even though the symptoms of bipolar affective disorder can be quite varied and complicated, the underlying genetics might actually have a more simple cause than we could have imagined.
Medical Research: What should clinicians and patients take away from your report?
Dr. Ginns: There is hope for bipolar patient that new drugs may be available sooner. For those of us searching for new ways to treat mood disorders, such as bipolar disorder, the finding of novel potentially druggable sonic hedgehog pathway targets is very exciting. There hasn’t been a really new drug treatment for bipolar disorder in decades. Our findings could revolutionize the way we diagnose and treat the disease.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Ginns: This breakthrough should help bipolar disorder research and the search for new treatments. We are already working with collaborators to unravel more details of the puzzle to identify changes in the sonic hedgehog signaling and related pathways that correlate with disease symptoms. We anticipate that additional studies of sonic hedgehog signaling in model systems and humans will help us gain a better understanding of the underlying biology and more effective treatments for bipolar and related disorders.
Citation:
E I Ginns, M Galdzicka, R C Elston, Y E Song, S M Paul and J A Egeland
Molecular Psychiatry , (14 October 2014) | doi:10.1038/mp.2014.118
Last Updated on October 21, 2014 by Marie Benz MD FAAD