MedicalResearch.com Interview with:
Elizabeth A. Thomas, Ph.D.
Associate Professor
Department of Molecular and Cellular Neuroscience
The Scripps Research Institute
Medical Research: What is the background for this study? What are the main findings?
Response: Increasing evidence has demonstrated that epigenetic factors can profoundly influence gene expression, and in turn, influence resistance or susceptibility to disease. Epigenetic drugs, such as histone deacetylase (HDAC) inhibitors, are finding their way into clinical practice, and are being proposed for therapeutic use in several neurological disorders. Our previous studies have shown that selective
HDAC inhibitors can cause beneficial effects in mouse models of Huntington’s disease, improving symptoms, and reducing severity of the disease. Our current studies show that one such compound can alter DNA methylation, an epigenetic mark that can be inherited, leading to changes in gene expression that are seen in the parent mouse exposed directly to the drug, as well as in offspring from the drug-treated male mice. Concurrent with these changes, we observed that offspring from drug-treated males shown improved disease symptoms, showing a delay in disease onset and a reduction of motor and cognitive symptoms that included improved performance in tests of balance, speed and memory.
These finding have significant implications for human health as they enforce the concept that ancestral drug exposure may be a major molecular factor that can affect disease outcome in a subsequent generation. One exciting aspect of our study is that the parental drug treatment made the offspring better, not worse, like other compounds known to cause transgenerational effects.
Dr. Dickey[/caption]
Audrey S. Dickey, Ph.D.
Assistant Professor
Department of Neurology, DUMC 2900
Durham, NC 27710
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: A drug already used to treat certain forms of cancer may also be an effective therapy for Huntington’s disease, according to a new study in the latest issue of Science Translational Medicine. The same study also increases our understanding of how this drug, and other medications like it, may offer hope for other neurodegenerative diseases like Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and Parkinson’s disease.
Huntington’s disease is a devastating, inevitably fatal disease, with no medications that slow or stop disease progression. In this study, mice with the equivalent of Huntington’s disease became more mobile, recovered from neurodegeneration, and lived longer after being treated with Bexarotene. The same research builds on a 2016 study where Dr. Al La Spada, Dr. Audrey Dickey and colleagues showed that the drug KD3010 is an effective treatment for Huntington’s disease in mice and in human patient neurons made from stem cells.
