Diagnostic and Mechanistic Validation of a Metabolic Biomarker Panel to Guide Therapeutic Interventions in Friedreich’s Ataxia

A key roadblock for all therapies has been a lack of biomarkers that can rapidly report on the efficacy and/or toxicity of a therapeutic intervention and the biochemistry of the disease. In Friedreich Ataxia, affected tissues, such as the heart or brain, cannot be assayed to quantify frataxin levels in response to therapies. The goal of this project is to conduct pre-clinical studies on a new set of biomarkers that Dr. Payne and Dr. O’Connell have discovered that reveal a distinct and highly specific metabolic profile in FA patients. Dr. Payne and Dr. O’Connell will test the hypothesis that a metabolic panel can be used as biomarkers for loss or recovery of FXN expression. They will first refine and optimize the biomarker panel using blood samples from 40 FA and 40 control subjects and then validate the performance of the defined biomarker panel using a larger, separate cohort of 60 FA and 60 control subjects. The investigators will subsequently evaluate the response of the biomarker panel to therapeutic intervention using TAT-FXN in a mouse model of FA. The short-term goal is to develop a biomarker panel for FA that quickly reports on disease state and efficacy of therapeutic intervention. The long-term goal of these studies is to understand the metabolic derangements in FA that determine patient outcomes.