MITOFUSIN AGONISTS TO TREAT NEURODEGENERATIVE DISEASE

线粒体融合蛋白激动剂治疗神经退行性疾病

• 批准号: 10290982
• 负责人: Gerald W. Dorn
• 金额: $ 7.85万
• 依托单位: MITOCHONDRIA IN MOTION, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-15 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10290982
• 关键词: Affect; Agonist; American; Amyotrophic Lateral Sclerosis; Biotechnology; Caregivers; Cells; Cessation of life; Charcot-Marie-Tooth Disease; Data; Disease; Disease Outcome; Disease Progression; Drug Kinetics; FDA approved; Family; Feasibility Studies; Future; Genetic; Genetic Risk; Healthcare; Huntington Disease; Individual; Intervention; Investigation; Lead; Manufactured Baseball; Metabolism; Mitochondria; Modeling; Morbidity - disease rate; Motion; Muscle Weakness; Muscular Atrophy; Mutation; Neurodegenerative Disorders; Other Genetics; Paralysed; Patients; Peripheral Nervous System Diseases; Pharmaceutical Preparations; Phase; Population; Property; Proteins; Publishing; Rare Diseases; Small Business Technology Transfer Research; Universities; Validation; Washington; blood-brain barrier penetration; effective therapy; first-in-human; humanized mouse; improved; in vivo; medical schools; mitochondrial dysfunction; mitochondrial fitness; mortality; mouse model; novel drug class; pre-clinical; response to injury; small molecule; trafficking; validation studies

Mitofusin agonists for the treatment of neurodegenerative diseases Gerald W Dorn II, MD Mitochondria in Motion, Inc. Washington University in St Louis School of Medicine Abstract: There are a number of rare neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS) and Huntington’s Disease (HD), for which there is no available or effective therapy and which lead to significant morbidity and mortality in affected populations. Mitochondria in Motion, Inc. will develop and produce investigational first-in-class small molecule mitofusin agonists, under an FDA approved IND, to treat these conditions. Mitofusin agonists enhance mitochondrial fitness, metabolism, and trafficking within cells, thus improving homeostatic functioning and injury-responses of cells adversely impacted by genetic mitochondrial dysfunction. Our published disease focus for mitofusin agonists was Charcot-Marie-Tooth disease type 2A, caused by mutations in our drug’s protein target, Mitofusin 2. Here, we hypothesized that intervention with a mitofusin agonist would have beneficial effects on other genetic peripheral neuropathies with a mitochondrial component, which is supported by our preclinical data in ALS and HD patient-derived cells. Thus, we will fill an unmet healthcare need and build a commercial enterprise to serve the ~20,000 Americans with ALS and the ~150,000 Americans suffering from or at genetic risk for developing HD, their caregivers and families. In this Phase I STTR we propose to optimize the pharmacokinetic properties of mitofusin agonists for systemic administration and blood-brain-barrier penetration (Aim 1), and complete in vivo feasibility and validation studies of mitofusin agonists to delay disease progression in the well characterized SOD1G93A mouse model of ALS. Our deliverable in Phase I will be a mitofusin agonist(s) ready for STTR Phase II IND-enabling studies and validation in an expanded number of orphan diseases, to prepare for future first-in-human trials.

治疗神经退行性疾病的丝裂酶激动剂