Duchenne muscular dystrophy

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

Duchenne Muscular Dystrophy – GNT 0004
Preclinical Phase I/II Pivotal Phase Approval

Genethon developed a gene therapy product in partnership with the Institute of Myology, the University of London and Nantes Gene Therapy Laboratory, and established a proof of concept in a canine DMD model.
Genethon is the sponsor of an ongoing international clinical trial.

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.

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.

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