Gene Therapy for Duchenne Muscular Dystrophy

What is Duchenne muscular dystrophy? 

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. Children with DMD lack a functional version of the dystrophin gene, which helps muscles stay healthy. As a result, their muscles break down and are replaced with fatty deposits over time.

As symptoms progress, children with DMD lose the ability to walk and usually require the use of a wheelchair by their early teens, as well as developing life-threatening heart and respiratory problems. Life expectancy ranges from teenage years to middle adulthood depending on genetic factors and the ability to receive supportive treatment from multiple specialists.

How is gene therapy used to treat Duchenne muscular dystrophy?    

DMD is caused by a defective gene for dystrophin, an essential protein for muscle strength. Individuals with DMD produce little to no dystrophin in their muscles.

Gene therapy for DMD is designed to induce production of a shortened but functional version of dystrophin, known as a micro-dystrophin protein.

While gene therapy doesn’t offer a cure for Duchenne muscular dystrophy and can't bring back muscle cells already lost, it shows promise in stabilizing the progression of symptoms and, in some individuals, improving strength and endurance at an age when children with Duchenne usually become weaker.

FDA Approves Gene Therapy Researched at CHOP for Children with Duchenne Muscular Dystrophy

On Thursday, June 22, the U.S. Food and Drug Administration (FDA) approved Elevidys, the first gene therapy for Duchenne muscular dystrophy (DMD), for patients with the disease between the ages of 4 and 5 years old. CHOP served as one of the clinical trial sites for Elevidys, developed by Sarepta Therapeutics. Learn more.

Duchenne muscular dystrophy treatment options at CHOP   

At CHOP, Duchenne muscular dystrophy patients are treated through our Neuromuscular Program.

Our physicians and scientists are active participants in clinical trials. We are tirelessly evaluating data that helps us better understand these diseases so we can create new and innovative treatments for neuromuscular disorders.

Children’s Hospital of Philadelphia currently offers the following therapies for Duchenne muscular dystrophy:

Exon Skipping – next generation treatments: The goal of exon skipping is to correct for missing exons in the DMD gene, thereby allowing the body to make a more functional form of the dystrophin protein. Approved treatments involve a weekly IV infusion therapy. They are available to children with DMD who have a confirmed mutation in the DMD gene that is amenable to exon 45, 51, or 53 skipping. Only about 30% of patients with DMD are eligible for this specialized treatment, and the impact of currently approved treatments on functional decline is modest. Next generation exon-skipping treatments aspire to target muscles more effectively and further increase levels of dystrophin to further improve stabilization of function with treatment.
Gene Therapy: The Food and Drug Administration (FDA) has approved Elevidys, the first gene therapy for DMD, for patients with the disease between the ages of 4 and 5 years old.This newly approved gene therapy delivers a copy of a gene that encodes a shortened, functional form of dystrophin, the gene that is mutated in DMD patients. Dystrophin is like a shock absorber for muscles, and without it, muscle deteriorates. The shortened microdystrophin in this gene therapy helps improve muscle health and slows muscle wasting.

What’s on the horizon for gene therapies for Duchenne muscular dystrophy

Alternative approaches to gene delivery are being developed. These approaches may have more targeted effects on the body’s muscles that need dystrophin or allow for even more functional versions of dystrophin to be produced.

Questions remain about whether gene therapy’s effects will be long-lasting in the various muscles of the body that need dystrophin. But there is growing knowledge about what safety risks or side effects can be expected in the short and long term for all people being treated and how their DMD can best be managed.

So far, it seems that some DMD gene mutations are more predisposed to immune reactions from gene therapy. Therefore, they’ve been excluded from dosing until researchers have studied them further and we’ve learned if they require specialized treatment approaches.

Alternative approaches such as gene repair via gene editing are also under development.