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

中间代谢罕见疾病治疗干预靶点的鉴定和验证

基本信息

批准号：
9200033
负责人：
Brian Robert Wamhoff
金额：
$ 43.38万
依托单位：
HEMOSHEAR THERAPEUTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-05 至 2017-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9200033
关键词：
Accounting Ammonia Area Biochemical Biocompatible Materials Biological Assay Biological Markers Biology Biotechnology Birth Carnitine Cells Cessation of life Chemistry Child Clinical Defect Development Disease Disease model Ensure Enzymes Failure to Thrive Future Genes Genetic Goals Health system Hepatic Hepatocyte Hereditary Disease Human In Vitro Intervention Laboratories Lead Legal patent Liver Liver diseases Metabolic stress Metabolism Methods Modeling Molecular Molecular Genetics Mutation Outcome Patients Phase Phenotype Propionates Rare Diseases Reagent Research Sampling Seizures Small Business Innovation Research Grant Staging Symptoms System Technology Testing Therapeutic Therapeutic Intervention Time Tissue Procurements Tissues Transplanted tissue Validation base biobank clinical Diagnosis clinically relevant drug development drug discovery effective therapy experience insight ketotic hyperglycinemia liver transplantation loss of function methylmalonic aciduria methylmalonyl-CoA decarboxylase mortality mouse model novel therapeutics programs propionyl-coenzyme A research study response screening success targeted treatment therapeutic development therapy development tool

项目摘要

Fast-Track SBIR: Identification and validation of targets for therapeutic intervention in rare diseases of intermediary metabolism defects. ABSTRACT 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 development, which contributes to a dismal record for development of new treatments. First, genetic mouse models do not faithfully mimic human rare diseases. Second, modeling liver diseases in vitro is challenging on account of the rapid loss of the liver-like phenotype of primary hepatocytes in vitro. For these reasons, target ID, validation and prioritization can be misleading and costly. In 2014, HemoShear, LLC and Children's National Health System formed a strategic partnership to systematize and accelerate discovery and treatments for rare diseases of the liver. HemoShear is an early stage biotechnology company with a patented technology for recreating human liver disease biology in the laboratory using human primary cells. The Division of Genetics and Metabolism at Children's is a premier research center with the nation's largest clinical program that studies and treats patients with liver rare diseases. Under this partnership, we have already shown that biomaterial from patients treated at Children's can be used to validate the rare disease system developed at HemoShear for the identification of targets for therapeutic development [Chapman et al, Mol. Gen. Metab., 2015]. This study will focus on the biochemical group of diseases called organic acidemias, specifically propionic acidemia and methylmalonic acidemia. These rare diseases have high early and late mortality rates, there are no primary therapies for these conditions and patients often undergo liver transplant to control symptoms. The purpose of this FastTrack SBIR is to identify, validate and prioritize targets for the future development of therapies to treat patients with intermediary metabolism defects in the liver.

快速通道SBIR：罕见病治疗干预靶点的识别和验证