Duchenne muscular dystrophy

Duchenne muscular dystrophy is the most common neuromuscular disease in children. It affects one in 3,500 boys at birth.

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.

Update – August 2021

Suspension of GNT 0004 microdystrophin gene therapy trial in Duchenne muscular dystrophy

RecruiThe gene therapy trial for the evaluation of the GNT 0004 product (microdystrophin) in Duchenne muscular dystrophy, sponsored by Genethon, was suspended due to a serious adverse event that occurred in a patient. Investigations are underway to understand the origin of this event, its possible link with the treatment or with another cause.

The patient, who was dosed with the gene therapy product in March 2021, showed a serious adverse event in late April. He was hospitalized and was released after his condition improved. He continues to be evaluated.

As soon as this incident occurred, Généthon, whose priority is patient safety, stopped recruiting for the trial and took the necessary steps with health authorities.

After all results of ongoing investigations are available, Genethon will share the data with the Data Monitoring Committee (DMC), an independent committee of experts, and will propose an appropriate protocol if necessary. The trial can only be resumed once the relevant health authorities have approved these amendments.. The natural history study, in which patients are included before the clinical trial, is maintained: the included patients continue to have regular appointments in their investigative centers and new patients may be included.

Find out more

>> For any questions, patients who are in the gene therapy trial or the natural history study should contact their investigating center

>> For general information, patients and their families can also contact the AFM-Telethon via the health referents or at the “Accueil Familles” number: 0 800 35 36 37

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