Galgt2 gene therapy / Nationwide Children's, Sarepta Therap - LARVOL DELTA

Gene Transfer Clinical Trial to Deliver rAAVrh74.MCK.GALGT2 for Duchenne Muscular Dystrophy (clinicaltrials.gov) - P1/2 | N=2 | Completed | Sponsor: Kevin Flanigan | Active, not recruiting ➔ Completed

Trial completion • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

A first-in-human phase I/IIa gene transfer clinical trial for Duchenne muscular dystrophy using rAAVrh74.MCK.GALGT2. (PubMed, Mol Ther Methods Clin Dev) - "Subject 2, treated at a younger age and at a higher dose, demonstrated an improvement over 24 months in NSAA score (from 20 to 23 points), an increase in 6MWT distance (from 405 to 478 m), and only a minimal increase in 100 m time (45.6-48.4 s). These data suggest preliminary safety at a dose of 1 × 10 vg/kg and functional stabilization in one patient."

Journal • P1/2 data • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Gene Transfer Clinical Trial to Deliver rAAVrh74.MCK.GALGT2 for Duchenne Muscular Dystrophy (clinicaltrials.gov) - P1/2 | N=2 | Active, not recruiting | Sponsor: Kevin Flanigan | Trial completion date: Jun 2022 ➔ Oct 2023

Trial completion date • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Gene Transfer Clinical Trial to Deliver rAAVrh74.MCK.GALGT2 for Duchenne Muscular Dystrophy (clinicaltrials.gov) - P1/2 | N=2 | Active, not recruiting | Sponsor: Kevin Flanigan | Trial completion date: Nov 2021 ➔ Jun 2022

Trial completion date • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

[VIRTUAL] Safety of Delivery of rAAVrh74.MCK.GALGT2 by Isolated Limb Infusion in Two Boys as a Surrogate Gene Therapy for Duchene Muscular Dystrophy (ASGCT 2021) - "Each were treated with oral prednisone from day -1 and through the weeks following infusion. In contrast, subject 2, treated at a younger age and at a higher dose, demonstrated an improvement over 24 months in the NSAA score (from 20 to 23 points), an increase in the 6MW distance (from 405 to 478 m), and only a minimal increase in 100 meter time (45.6 to 48.4 sec), suggesting stability or improvement. These limited data suggest the preliminary safety of delivery of a systemic dose of 1 x 1014 vg/kg, and suggest efficacy at the higher dose in younger patients."

Clinical • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Short-term treatment of golden retriever muscular dystrophy (GRMD) dogs with rAAVrh74.MHCK7.GALGT2 induces muscle glycosylation and utrophin expression but has no significant effect on muscle strength. (PubMed, PLoS One) - "Serum chemistry, hematology, and cardiac function measures were largely unchanged by treatment. Cumulatively, these data show that short-term intravenous treatment of GRMD dogs with rAAVrh74.MHCK7.GALGT2 at high doses can induce muscle glycosylation and utrophin expression and may be safe over a short 3-month interval, but that such treatments had only modest effects on muscle pathology and did not significantly improve muscle strength."

Journal • Duchenne Muscular Dystrophy • Fibrosis • Genetic Disorders • Hematological Disorders • Immunology • Muscular Dystrophy

rAAVrh74.MCK.GALGT2 Demonstrates Safety and Widespread Muscle Glycosylation after Intravenous Delivery in C57BL/6J Mice. (PubMed, Mol Ther Methods Clin Dev) - "Using intramuscular delivery, GALGT2-induced muscle glycosylation was increased in Cmah-deficient mice, which have a humanized sialoglycome, relative to wild-type mice, suggesting that use of mice may underestimate GALGT2 activity in human muscle. These data demonstrate safety and high transduction of muscles throughout the body plan with i.v. delivery of rAAVrh74.MCK.GALGT2."

Journal

rAAVrh74.MCK.GALGT2 Protects against Loss of Hemodynamic Function in the Aging mdx Mouse Heart. (PubMed, Mol Ther) - "Intravenous treatment of mdx mice with rAAVrh74.MCK.GALGT2 at 2 months of age significantly improved stroke volume and cardiac output compared to mock-treated mice analyzed at 17 months, both at rest and after stimulation with dobutamine. rAAVrh74.MCK.GALGT2 treatment of mdx heart correlated with increased glycosylation of α-dystroglycan with the CT glycan and increased utrophin protein expression. These data provide the first demonstration that GALGT2 overexpression can inhibit the loss of cardiac function in the dystrophin-deficient heart and, thus, may benefit both cardiac and skeletal muscles in DMD patients."

Journal • Preclinical

Gene Transfer Clinical Trial to Deliver rAAVrh74.MCK.GALGT2 for Duchenne Muscular Dystrophy (clinicaltrials.gov) - P1/2; N=6; Active, not recruiting; Sponsor: Kevin Flanigan; Recruiting ➔ Active, not recruiting; Trial completion date: Nov 2020 ➔ Nov 2021

Clinical • Enrollment closed • Trial completion date