Amplo Biotechnology Inc

Targeted DOK7 Gene Therapy for Congenital Myasthenic Syndromes - Project Summary Congenital Myasthenic Syndromes (CMS) Are a Group of Genetically and Phenotypically Heterogeneous, Neuromuscular Transmission Disorders Characterized by Muscle Weakness (myasthenia) That Worsens With Physical Exertion. DOK-7 (downstream of Tyrosine Kinase 7) Is a Key Regulator of Neuromuscular Junction (NMJ) Formation. Homozygous Loss-of or Reduction Of-function Mutations in the Human DOK7 Gene Underlie a Limb-girdle Type of CMS Characterized by NMJS That Are About Half the Normal Size. DOK-7 CMS Is an Orphan Disease Estimated to Affect 3,600 People Worldwide. Patients With DOK-7 CMS Have a Decreased Quality of Life (QOL) Due to Exercise Intolerance, Dependency on Intermittent Respiratory Support, And/or Tube Feeding by Adulthood (2/3 of the Patients). Moreover, About Half of the Patients Will Need a Wheelchair for Ambulation, and the Other Half Will Require Walking Aids. No Cure nor Standardized Treatment Has Been Yet Developed for DOK-7 CMS. While Forms of CMS Are Managed Through the Administration of Acetylcholine (ACHE) Inhibitors, DOK-7 CMS Is Refractory and Can Deteriorate If Treated With Ache Inhibitors. Symptoms Ameliorations for DOK-7 CMS Is Achieved by Recurrent Administration of Ephedrine and Albuterol, SS2-ADRENERGIC Receptor Agonists, Which Provide Suboptimal Symptom Management for Some Patients. Moreover, Prolonged Exposure to SS2-ADRENERGIC Receptor Can Cause Tachycardia Cardiac Ischemia, Heart Failure, Cardiomyopathy, and Increased Inflammatory Response. Amplo Biotechnology Is Developing AMP-101, the First Gene Therapy Product for DOK-7 CMS. the Treatment Is Based on a Recombinant Adeno-associated Virus Serotype 9 (AAV9) Vector Carrying the Human DOK7 Gene. Preliminary Results in a DOK-7 CMS Mouse Model Show That AMP-101 Can Enlarge NMJS, Improve Motor Function, and Extend the Very Limited (20 Days After Birth) Life Span of Dok- 7 CMS Mice to the Level of WT Controls. the New Product Will Enable a Shift in the Current Clinical Practice From Chronic Administration of Drugs to Alleviate Symptoms to a One-off Treatment, Administered Through a Single Intravenous Injection. the Solution Will Allow Physicians to Treat the Entire Affected Population, Curing Adult Disease, and Stopping Disease Progression in Children. the Goal of This Sbir Fast-track Project Is to Validate the Efficacy and Safety of Using AMP-101 for DOK-7 CMS. Amplo Will Use Phase I Activities to Perform a Pre-clinical Dose-finding and Safety Study in DOK-7 CMS Mice. the Outcome of Phase I Activities Will Be Used to Direct Pivotal Dmpk/adme and Toxicology Studies in Non-human Primates (NHP) in Phase Ii, When Manufacturing, Quality, and Stability Procedures Will Also Be Defined. the Experimental Plan Proposed Has Been Validated by the Fda in a Recent Pre-ind Query and an Ind Application Will Be Submitted at the End of the Project.