Identification and validation of targets for therapeutic intervention in rare diseases of intermediary metabolism

Fast Track SBIRIdentification and validation of targets for therapeutic intervention in rare diseases of intermediary metabolism defectsABSTRACT There are very few reliable methods to study and understand the biology of liver rare diseases in the laboratory for the purpose of drug discovery and developmentwhich contributes to a dismal record for development of new treatmentsFirstgenetic mouse models do not faithfully mimic human rare diseasesSecondmodeling liver diseases in vitro is challenging on account of the rapid loss of the liver like phenotype of primary hepatocytes in vitroFor these reasonstarget IDvalidation and prioritization can be misleading and costlyInHemoShearLLC and Childrenandapos s National Health System formed a strategic partnership to systematize and accelerate discovery and treatments for rare diseases of the liverHemoShear is an early stage biotechnology company with a patented technology for recreating human liver disease biology in the laboratory using human primary cellsThe Division of Genetics and Metabolism at Childrenandapos s is a premier research center with the nationandapos s largest clinical program that studies and treats patients with liver rare diseasesUnder this partnershipwe have already shown that biomaterial from patients treated at Childrenandapos s can be used to validate the rare disease system developed at HemoShear for the identification of targets for therapeutic developmentChapman et alMolGenMetabThis study will focus on the biochemical group of diseases called organic acidemiasspecifically propionic acidemia and methylmalonic acidemiaThese rare diseases have high early and late mortality ratesthere are no primary therapies for these conditions and patients often undergo liver transplant to control symptomsThe purpose of this FastTrack SBIR is to identifyvalidate and prioritize targets for the future development of therapies to treat patients with intermediary metabolism defects in the liver Fast Track SBIRIdentification and validation of targets for therapeutic intervention in rare diseases of intermediary metabolism defectsNARRATIVE There are very few reliable methods to study and understand the biology of liver rare diseases in the laboratory for the purpose of drug discovery and developmentwhich contributes to a dismal record for development of new treatmentsInHemoShearLLC and Childrenandapos s National Health System formed a strategic partnership to systematize and accelerate discovery and treatments for rare diseases of the liverUnder this partnershiptissue and biomaterial from patients treated at Childrenandapos s can be used to validate the rare disease system developed at HemoShear for the identification of targets for therapeutic developmentThis study will focus on the biochemical group of diseases called organic acidemiasThese rare diseases have high early and late mortality ratesthere are no primary therapies for these conditions and patients often undergo liver transplant to control symptomsThe purpose of this FastTrack SBIR is to identifyvalidate and prioritize targets for the future development of therapies to treat patients with intermediary metabolism defects in the liver