BLR&D Research Career Scientist Award Application

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The major area of our research is to help understand the causes of, and development treatments for neurodegenerative diseases and conditions, in particular Alzheimer’s Disease (AD) and Multiple Sclerosis (MS). This work includes repurposing drugs that are FDA-approved for other indications but we show can provide benefit in animal models of AD and MS, making it easier to bring them to the clinic. A better understanding of how these diseases start and evolve, and identification of interventions will help reduce disease symptoms, as well as social and economic burdens. Our MS studies currently funded by a Merit grant have expanded into the area of genetic risk factors that may predispose one to developing MS, based on our findings of a novel nucleotide variant in one particular gene. We are now determining how the variant increases risk using cell cultures and a mouse model that we developed to replicate the human variant, and testing drugs to see if they can minimize its effects. We are also testing if this variant, or others, is present at higher frequency in certain veteran populations, including in African American, Hispanic, and Caucasian cohorts. At the same time in work funded by the National MS society, we are testing a novel compound in a mouse model of MS we believe will reduce neuronal damage and also increase the myelin sheath that surrounds and protections nerve cells. We are also working on a project to evaluate the consequences of excessive alcohol consumption on the development of AD. We found that exposing brain ‘support’ cells (glial cells) to ethanol reduces their ability to clear amyloid plaques; we plan to extend those cell studies to a mouse model of AD. We have also been funded to carry out studies that may have particular importance to our active military as well as veteran population, namely studies on possible neurological damage caused by commonly used anti- coagulants (e.g.warfarin), and also more potent ‘superwarfarins’ that are used as rodenticides, but unfortunately have also been used in military situations. We are developing methods using FDA-approved drugs, we hope will prevent the toxic effects of these drugs as well as long term consequences.