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