DICHLOROACETATE TREATMENT OF CLA PRESENTING IN INFANCY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our primary objective is to continue evaluating the chronic safety of dichloroacetate-DCA as a potential treatment for one patient with a certain heretofore untreatable form of congenital lactic acidosis-CLA, starting treatment in the infancy period of life (defined as the period from birth to two years of age). Currently we have a Phase III, open label study involving 6 patients who previously participated in a phase 3, double-blind, phase A, trial, in which they received 25mg/kg/day of DCA for up to 18 months. Those subjects continue in the Dichloroacetate Treatment of Congenital Lactic Acidosis study, with follow up appointments every 6 months, so we may finalize the data collection process A secondary objective is to determine the genotype of this subject. There are four polymorphisms of the enzyme responsible for the principal route of DCA biotransformation, one of which has a 10-fold higher Km for DCA. Consequently, DCA kinetics and biotransformation may be significantly different in subjects who have this high KM genotype.