Microdystrophin Gene Therapy in Duchenne Muscular Dystrophy
Research type
Research Study
Full title
Microdystrophin (GNT0004) Gene Therapy Clinical Trial in Duchenne Muscular Dystrophy A phase I/II/III study with a dose determination part followed by an efficacy and safety evaluation, quadruple blind placebo-controlled part and then by a long term safety follow up part, in ambulant boys.
IRAS ID
287014
Contact name
Francesco Muntoni
Contact email
Sponsor organisation
Genethon
Eudract number
2020-002093-27
Clinicaltrials.gov Identifier
Duration of Study in the UK
8 years, 0 months, 0 days
Research summary
Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive neuromuscular disorder caused by mutations in the dystrophin gene. DMD is affecting around 1/5000 live males, it results in progressive weakness, loss of ambulation and death by the third–fourth decade of life. DMD affected individuals develop muscle weakness in the first years of life. Most are diagnosed before the age of 5 years, when their physical ability diverges markedly from that of their peers. They begin to lose walking distance around age 7, progress to a loss of ambulation in the preteenage and early-teenage years. At cessation of walking, more severe deformities occur, related to habitual posture in the wheelchair. Pain in the muscles is common. Respiratory failure results from restrictive defect.
Pulmonary growth is stopped and the vital capacity decreases after the age of ten. Cardiac failure is a major reason for death between twenty and forty years of age.
There is an unmet medical need for the treatment of DMD, there is no cure and standard of care is mainly limited to corticosteroids and assistive devices. DMD requires a multidisciplinary management that includes assistive devices, rehabilitative management, treatment of complications, and genetic counselling.
In recent years, a number of experimental therapeutic approaches have been developed aiming to re-establish the expression of dystrophin, restore the absent dystrophin protein in muscles. There are 3 authorized synthetic genetic therapies for the treatment of DMD. They have shown some immediate beneficial effects but needs to be confirmed for long-term use.
GNT0004 is a gene therapy, aims to restore functional dystrophin to the muscle and heart. It’s designed to deliver in DMD patient, whatever their genetic defect, an optimized microdystrophin protein. Although not the full dystrophin protein, would significantly delay or markedly slow down the progression of the disease over time.REC name
London - West London & GTAC Research Ethics Committee
REC reference
20/LO/1222
Date of REC Opinion
22 Jan 2021
REC opinion
Further Information Favourable Opinion