Rapid Haplotyping procedure for determining the response of patients to DCA

DESCRIPTION provided by applicant Dichloroacetate DCA has therapeutic potential in treating several rare and common life threatening diseases of children and adults These include congenital pyruvate dehydrogenase complex deficiency PDCD pulmonary arterial hypertension PAH diabetes heart disease cancer and other diseases in which it has been investigated as a therapeutic However DCA is potentially neurotoxic limiting its clinical use Medosome Biotec LLC MBT and its research partners at the University of Florida UF believe a significant market exists to develop and commercialize a kit for GSTZ genotyping for use in administering DCA for the treatment of PDCD and other disorders benefitted by DCA Medosome Biotec and its research partners at University of Florida Drs Peter Stacpoole and Taimour Langaee have used pyrosequencing techniques to identify haplotype variations in human GSTZ that confer variable rates of plasma clearance of DCA Dr Stacpoole discovered the pharmacodynamic properties of DCA and has led in its use as an FDA declared Orphan Product for rare diseases The only clinically limiting adverse effect of chronic DCA is reversible peripheral neuropathy Dr Stacpoole has shown that this toxicity may be prevented by personalized dosing of DCA based on GSTZ haplotype status These promising studies serve as the basis for the central SBIR hypothesis that GSTZ haplotype based dosing of DCA has the potential to provide safe and effective treatment for PDCD and other diseases for which DCA may be beneficial Accordingly the goal of this SBIR Phase I grant will be to develop and apply a prototype commercial kit for determining GSTZ haplotypes that can be used by physicians for personalized dosing of DCA for the treatment of PDCD and other diseases responsive to DCA administration The Specific Aims of the proposal will be to Develop standard operating procedures SOPs for GSTZ haplotype analysis based on Single Nucleotide Polymorphisms SNPs and a companion kit for collecting samples and health information from prospective patients Identify and analyze the frequency of GSTZ haplotypes in a healthy adult population using the kit and analytic procedures developed in Specific Aim and Establish the accuracy and validity of the GSTZ haplotype analysis by determining the plasma pharmacokinetics PK of DCA in a subset of subjects identified in Specific Aim who are predicted to be slow or fast DCA metabolizers based on GSTZ haplotype analysis PUBLIC HEALTH RELEVANCE Dichloroacetate DCA has therapeutic potential in treating several rare and common life threatening diseases of children and adults However DCA is potentially neurotoxic limiting its clinical use However Medosome Biotec LLC and its research partners at University of Florida will have successfully developed genotyping procedure that will allow for personalized dosing of DCA which will reduce adverse reactions and support the development of DCA as a safe and effective treatment for many diseases