Personalized dosing of dichloroacetate for the treatment of rare and common diseases

Pyruvate dehydrogenase complexPDCdeficiencyPDCDis a rare disease of mitochondrial energy failure in which the life of expectancy of affected children is severely truncatedTreatment of PDCD remains a seriousunmetchallengeThere has never been a controlled trial of any intervention for PDCDthusthere is no proven therapy for affected patientsDichloroacetateDCArepresents the first targeted therapy for PDCD by stimulating residual PDC activity in all tissuesincluding the central nervous systemCNSBased on both controlled trials and open label studies of DCA in mitochondrial diseasesMedosome BiotecLLCMBTand its research partners at the University of FloridaUFDrsPeter Stacpoole and Taimour LangaeePD PIs for Phase Idetermined the data were sufficiently compelling to justify a pivotal phasetrial of DCA in this diseasefor which DrStacpoole at UF and DrJ L PThompson at Columbia University are PD PIsIn response to these promising studies and extensive potential commercial marketMedosome BiotecLLCMBTand its research partners at UF have developed a central STTR hypothesis that GSTZhaplotypebased dosing of DCA has the potential to provide safe and effective treatment for PDCD and other diseases for which DCA may be beneficialThe team proposes a STTR Fast Track to test thisPhase IDevelop a procedure for GSTZhaplotypes analysisreferred to as Halotype Identification Procedure or HIPthat can be used by physicians for personalized dosing of DCAPhase I Specific AimEstablish the accuracy and validity of the GSTZhaplotype analysis by determining the plasma pharmacokineticsPKof DCA in subjects identified in Specific Aimwho are predicted to be slow or fast DCA metabolizersbased on GSTZhaplotype analysisPhase IIUse the new procedure to accurately genotype and dose stratify PDCD patients for the PhasetrialThe team will test these hypotheses by accomplishing the following Phase II Specific AimsConduct a pivotal Phasetrialconsistent with FDA guidelinesthat could lead to the agency s approval of DCA for PDCDusing the procedure developed during Phase I to provide personalizedgenetics based dosing to improve the safety of chronic DCA treatmentandCommercialize the kit and analytic procedures for use in PDCD and other diseases amenable to DCA treatment