First gene therapy for Duchenne muscular dystrophy administered

A five-year-old boy has become the first patient to receive the recently FDA-approved gene therapy to treat his Duchenne muscular dystrophy (DMD).

The rollout of the first gene therapy that targets DMD, co-developed by Jerry Mendel (Nationwide Children’s Hospital; OH, USA) and Louise Rodino-Klapac (Sarepta Therapeutics, MA, USA) has begun at the Abigail Wexner Research Institute of the Nationwide Children’s Hospital. The therapy, named ELEVIDYS (SRP-9001), will be used to treat young patients in the same hospital where it was initially developed. It is one of eight gene therapies granted a license by the FDA and its implementation will alleviate the effects of the progressive neuromuscular disorder.

DMD is an X-linked genetic condition in which dysfunctional copies of the DMD gene result in insufficient levels of dystrophin protein, which causes atrophy and muscle weakness. The current suite of treatments for DMD targets the symptoms of the condition, through steroid cream and mobility exercises, but are limited in their efficacy.

In order to address this shortfall in the standard of care, Mendel and Rodino-Klapac co-developed the novel drug, ELEVIDYS. The therapeutic aims to combat the dystrophin shortage in people with DMD by supplementing cells with a gene that encodes for a shortened but functional form of the protein called Elevidys micro-dystrophin.

These micro-dystrophin genes are encapsulated in an adeno-associated virus serotype, which serves as their delivery vesicle. Furthermore, the treatment is administered in a single intravenous dose, in contrast to other therapeutics for the condition which require continual treatments.

Due to the considerable unmet treatment need for this condition, ELEVIDYS was accepted onto, and licensed by, the FDA’s Accelerated Approval pathway. As such, the clinical benefit of ELEVIDYS is yet to be proven; however, a randomized clinical trial of the drug has demonstrated that its administration leads to an increase in the expression of Elevidys micro-dystrophin protein observed in a cohort of 4-5 year olds with DMD.

The treatment of the first patient to receive the drug, five-year-old Gideon Griffiths, marks a “meaningful day not only for these first families, but for families battling DMD everywhere,” commented Mendell. This development may well galvanize the use of gene therapies to treat DMD while encouraging the ongoing development of gene therapies for other genetic disorders.