Diversity Supplement for Ighodaro: Fibrate modulation of microRNA107

We are writing to request supplemental funding for the R01 grant (AG042419, which runs through June 2016; Jicha and Nelson PIs) to support 18 months (Jan. 1 2015 -June 30, 2016) of the graduate work of Ms. Eseosa Ighodaro. Eseosa is a very promising MD/PhD student who is an African- American interested specifically in a research career in academic clinical neuroscience, and who is working in the lab of one of the grant PIs (Dr. Nelson). The funding period corresponds to remaining time of the funded R01. The proposed mentoring will expand her skill set and facilitate the submission of competitive proposals related to neuroscience clinical trials research. There currently is no funding on that grant for a graduate student. Because of her interest in studying clinical neuroscience, cerebral vascular pathology, and conducting clinical trials, she will augment the R01 parent grant by using collected data from the R01 protocol to test the hypothesis that gemfibrozil affects biomarker endpoints in persons with vasc ular (as opposed to AD) pathology. This grant supports a Phase I clinical trial to study gemfibrozil as a potential therapy for Alzheimer's disease (AD). Gemfibrozil is a safe, orally-administered, "fibrate" (PPAR-alpha agonist) drug that is FDA-approved for the treatment of hyperlipidemia in aged individuals. Value-added subproject proposed by Eseosa: evaluate a subset of patients that meet two criteria: 1. Lack AD-type CSF biomarkers; 2. Show MRI evidence of neurodegeneration and/or vasculopathy. These AD-negative patients are of special interest because of the possibility their brains harbor vascular pathology. The specific hypothesis to be tested is whether miRNA biomarkers and longitudinal cognitive trajectory are changed by a PPAR-alpha agonist in non-AD vascular pathology. Preliminary data indicate we will have statistical power to at least provide publishable preliminary data that would also facilitate future studies. This represents an exciting experimental context to study the potential impact (including cognitive trajectory and miRNA biomarkers) of gemfibrozil in vascular brain disease, from biomarkers to cognitive status. This experiment was actually suggested by the reviewers of the R01 parent grant, but, there was inadequate personnel to study this in a focused way, so we are extremely pleased that Eseosa will take this project on.