Author Interviews, Neurological Disorders / 07.12.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Genetic Research, Neurological Disorders / 26.08.2016

MedicalResearch.com Interview with: Lee Henderson, Ph.D. CEO Vybion, Inc. Ithaca, NY 14852 Lee Henderson, Ph.D. CEO, Vybion, Inc. Ithaca, NY 14852 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Huntington’s disease (HD) is a progressive and fatal neurodegenerative disease characterized by loss of both cognitive and motor function as a result of neuron loss primarily within the brain striatum. HD is directly caused by the expansion of CAG repeats in the huntingtin gene resulting in an expanded glutamine region (polyQ) near the N-terminus of the protein. Age of disease onset and the rate of progression is directly correlated to the size of the expansion with pathology observable at 35-70 repeats in adults and greater in juvenile onset. During normal turnover and degradation of the huntingtin protein, the N-terminal polyQ-containing fragments drive pathology and aggregate formation in cells. The direct link to progression has been described by several laboratories using cell-based and animal model studies and confirmed in humans as the binding of these N-terminal fragments to DNA and transcription factors that result in widespread gene dysregulation in neurons. (more…)
Author Interviews, Genetic Research, Karolinski Institute, Nature, Neurological Disorders / 11.05.2015

MedicalResearch.com Interview with: Kristina Bečanovič Ph.D. Department of Clinical Neuroscience Karolinska Institutet, Stockholm, Sweden Medical Research: What is the background for this study? Dr. Bečanović: While the symptoms normally debut in middle-age, there is wide individual variation in how Huntington disease manifests itself, and even though two people carry the exact same genetic mutation that codes for the huntingtin protein, there can be up to a 20-year difference in onset of motor symptoms. This suggests that genetic variants, transcription factors and environmental factors could contribute to the observed differences in disease expressivity. As the identification of regulatory factors of the huntingtin gene would be targets for therapeutic intervention, we set out to study the regulation of the huntingtin gene as it has not been well-known which factors regulate the expression levels. We were interested in identifying both genetic variants and transcription factors that are of importance for gene regulation. We therefore used DNA from Huntington disease patients to study the regulation of the huntingtin gene promoter in cells. (more…)
Author Interviews, Neurological Disorders / 04.03.2015

MedicalResearch.com Interview with: Dr. Richard H. Myers Ph.D. Department of Neurology and Genome Science Institute Boston University School of Medicine, Boston, MA MedicalResearch.com Interview with: Dr. Richard H. Myers Ph.D. Department of Neurology and Genome Science Institute Boston University School of Medicine, Boston, MA MedicalResearch: What is the background for this study? What are the main findings? Dr. Myers: Andy Hoss, who is a graduate student in my group is the primary investigator for this project. We are investigating changes that occur in the brain of individuals who had Huntington's disease. We were focused on studying regulatory mechanisms that control the levels of messenger RNAs (mRNAs) in the brain, since that is an area that has been implicated in this disease. MicroRNAs (miRNAs) are known to target mRNAs for degradation or to be sequestered for storage and later use. A few limited studies of microRNAs had been done, but we sought to measure the levels of all of the miRNAs present in the brains of persons with Huntington's disease and in controls using next-generation sequencing. (more…)
Author Interviews, Genetic Research, Neurological Disorders, PNAS, Scripps / 26.12.2014

Elizabeth A. Thomas, Ph.D. Associate Professor Department of Molecular and Cellular Neuroscience The Scripps Research Institute 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. (more…)
Author Interviews, Neurological Disorders, Scripps / 30.10.2014

Srinivasa Subramaniam, Ph.D., Assistant Professor Department of Neuroscience The Scripps Research Institute Jupiter, Florida 33458 MedicalResearch.com Interview with: Srinivasa Subramaniam, Ph.D., Assistant Professor Department of Neuroscience The Scripps Research Institute Jupiter, Florida 33458   Medical Research: What is the background for this study? What are the main findings? Dr. Subramaniam: Huntington’s disease (HD) is a genetic disorder occurs due to a mutation in a protein called huntingtin (mHtt), which affects 5-10 people per 100000 populations worldwide. Our research revolves around the question— why mutant huntingtin despite its ubiquitous expression through out the body selectively affects brain regions such as striatum, a region that regulates voluntary movement. We now found that mHtt activates a protein kinase complex, mammalian target of rapamycin complex 1 (mTORC1), which is required for normal functions such as translation of genes into proteins and also organelle recycling. We found the mTORC1 activation is so robust and sustained in the striatum that lead to the severe motor disabilities and premature death of HD mice. Our study indicates a functional relationship between huntingtin and mTOR the developmentally important genes with implication in Huntington’s disease pathogenesis. (more…)