Duchenne muscular dystrophy is the most common neuromuscular disease in children. It affects one in 3,500 boys at birth.
Design of the gene therapy product, proof of concept in a DMD canine model. Genethon sponsor of the ongoing multicenter clinical trial. Collaboration and license agreement with Sarepta.
What is Duchenne muscular dystrophy?
Duchenne muscular dystrophy is the result of a mutation or deletion of the gene encoding dystrophin, located on the X chromosome. Non-expression or very abnormal dystrophin expression causes the muscle fibers to weaken, resulting in accelerated destruction of the muscle tissue. This leads to general, progressive, irreversible and severe loss of motor function. Sufferers usually lose the ability to walk between the ages of 10 and 13 years, and by the time they reach adolescence they require respiratory assistance. The involvement of the heart muscle can impact survival. 150 to 200 young boys are diagnosed with Duchenne muscular dystrophy each year in France.
Duchenne muscular dystrophy: Genethon’s role
Genethon has conducted several projects that aim to treat Duchenne muscular dystrophy.
The most advanced product to date is GNT-0004, which comes from the teams at Genethon, those at the Institute of Myology (Paris) and at the University of London (Prof. George Dickson, Royal Holloway), based on use of an AAV (Adeno Associated Virus) vector carrying the transgene coding for micro-dystrophin.
Since the dystrophin gene is very large, it is technically impossible to insert the complete DNA of the dystrophin into this type of vector.
The therapeutic strategy therefore involves providing a gene encoding a shortened but functional form of this protein (micro-dystrophin).
The production of this micro-dystrophin protein in the patient’s muscles could allow us to treat all patients suffering from Duchenne muscular dystrophy.
Duchenne muscular dystrophy: what’s happening today?
A Baseline study (France/United Kingdom/Israel/United States) is currently ongoing. The aim of this study is to track the disease’s natural evolution to determine the criteria that will allow the efficacy and safety of GNT-0004 to be demonstrated. Around one hundred young boys still able to walk – aged 5 to 9 – will be tracked for between 3 months and 3 years. This study will allow us to identify children who may be included in the GNT-0004 therapeutic trial but also indicate the outlines of the parameters assessed.
The clinical trial for GNT-0004 has received authorization from the ANSM in France and from the MHRA in Great Britain.
For this program Genethon has entered into a partnership with US-based company Sarepta Therapeutics, a major player in innovative therapies for Duchenne muscular dystrophy.
In April 2021, the trial, that had started in France, was suspended due to a serious adverse event that occurred in a patient. Genethon carried out investigations to understand the origin of this event and proposed amendments to the protocol to the Health Authorities. The amended protocol was validated by the ANSM, the French National Agency for Medicines and Health Products Safety, on March 1st, 2022 and by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK on March 16th , 2022.
Find out more
- Genethon announces First Patient dosed in Clinical Trial of Investigational Gene therapy GNT 0004 for Duchenne Muscular Dystrophy (04/20/2021)
- Genethon gets the green light from the ANSM to start an innovative gene therapy trial for Duchenne muscular dystrophy (12/02/2020)
- Journée mondiale de la myopathie de Duchenne : cap vers un essai de thérapie génique en France [in French]
- Genethon strengthens its collaboration with Sarepta Therapeutics for the development of the gene therapy product GNT0004 in Duchenne muscular dystrophy (01/09/2020)
- Restore muscle strength in Duchenne muscular dystrophy through microdystrophin (07/25/2017)
- New partnership for the treatment of Duchenne muscular disease (DMD) (06/21/2017)