Congenital pyruvate dehydrogenase complex (PDC) deficiency (PDCD) is a life-threatening mitochondrial disease of metabolic integration in which the efficient conversion of carbohydrate fuel into energy is perturbed. There are no proven therapies for PDCD. However, dichloroacetate (DCA) represents targeted potential therapy for this disease by stimulating residual PDC activity, decreasing hyperlactatemia and improving mitochondrial energetics. This background and our preliminary data suggest that DCA may benefit the clinical status of PDCD children. We have worked closely with the FDA and a parent-driven organization to develop an appropriate study design and identify prospective subjects. We now propose to undertake a 4 year phase 3 clinical trial to test the hypotheses that oral DCA will improve at-home functionality of affected children compared to placebo and will be well-tolerated and safe for chronic use. Our primary endpoint will be based on an improved clinical status, as determined by a novel, Observer Reported Outcome (ObsRO) measure. Our secondary endpoints will include 1) confirmation of better clinical outcome by the Karnofsky/Lansky performance scale of home functionality in children with life- threatening disease; and 2) decreased lactatemia.
Dichloroacetate (DCA) holds promise as the first potential therapy for pyruvate dehydrogenase complex deficiency (PDCD, a life-threating genetic disease in which cells die from a lack of energy created by mitochondria, the cells ?power house.? We plan to conduct the first randomized controlled trial of DCA in young children (aged 1 month ? 18 years) with PDCD, in collaboration with academic health centers across the U.S. If the trial shows DCA is safe and effective, it could lead to its use as the first FDA-approved drug for this devastating neurodegenerative disease.