Gene Therapy for Duchenne Muscular Dystrophy

Gene therapy has become one of the most closely watched areas of research in Duchenne Muscular Dystrophy (DMD).

Duchenne Muscular Dystrophy (DMD) is caused by changes in a gene called DMD. This gene provides the instructions to make dystrophin, a protein that helps keep muscle cells strong and healthy.

In recent years, scientists have been investigating approaches that could target this genetic problem. Some of the main approaches include gene therapy, exon skipping, and nonsense mutation readthrough. Each of these methods uses a different strategy to help the body make dystrophin or restore some of its function.

In this blog, we’ll take a closer look at gene therapy: how it works, which therapies have already been approved by health authorities, and what treatments are still being tested in research studies. We’ll also explore what the typical approval process looks like for investigational therapies like gene therapy.

This blog is for anyone who wants to better understand gene therapy for Duchenne and the progress being made in this area.

What Causes Duchenne Muscular Dystrophy?

Duchenne is a rare genetic condition that progresses over time. It mainly affects boys, with an estimated 1 in 3,500 to 5,000 boys worldwide born with Duchenne each year. It is caused by mutations (changes in the DNA) in a gene called DMD. This gene is responsible for producing the dystrophin protein, which helps keep muscles strong and healthy. ¹

This protein works like a shock absorber in muscle cells. It protects the tiny strands inside muscles (known as muscle fibers) from damage when muscles tighten and relax (called muscle contractions). Without enough dystrophin, the muscles are more likely to get injured during everyday activities. ¹

When the muscles are damaged, the body tries to repair them. Over time, these repair cycles become less effective. This leads to chronic inflammation, then to progressive scarring of the muscle tissue (fibrosis), and eventually to a loss of muscle function. ¹

Looking for more information about what causes Duchenne, how it’s diagnosed, and the signs to look for? Read our blog ‘Living with Duchenne Muscular Dystrophy: Treatments and Care Essentials’.

What Types of Dystrophin Gene Mutations Lead to Duchenne?

Genes carry instructions, like recipes, for making proteins. Proteins are essential molecules that perform a wide range of functions throughout the body. A mutation is a change in these instructions. Some mutations have no effect, but others can change how the body works or increase the risk for certain diseases. ^{1, 2, 3}

Duchenne is caused by mutations within the DMD gene. This gene contains 79 sections, known as exons. Having so many exons makes it one of the largest genes in the human body. Because it’s so large, many different types of mutations can happen along this gene.

The most common types of dystrophin gene mutations that cause Duchenne include:

• Deletions (60-70% of the cases): One or more exons are missing. ^{4, 5, 6}
• Large duplications (10% of the cases): One or more exons within the gene are duplicated, leading to extra copies of those segments. ^{4, 5, 6}
• Point mutations (15-30% of the cases): Smaller changes in the gene that do not involve an entire gene section or exon. The most common form is a ‘nonsense variant’, which creates a “stop signal”, prematurely ending the production of dystrophin.^{4, 5, 6}

The exact type of mutation can affect how much dystrophin the body makes. In some cases, the mutation leads to a related but milder condition called Becker Muscular Dystrophy (BMD). In Becker, the body can still make some dystrophin, just in a shorter or less effective form. This means muscle weakening happens more slowly, and symptoms are usually less severe.

If you want to know more about Becker Muscular Dystrophy, visit our blog ‘Navigating Becker Muscular Dystrophy: Symptoms, Diagnosis, and Treatment Options’.

What is gene therapy for Duchenne Muscular Dystrophy?

Gene therapy is a type of treatment that aims to fix the genetic problem that causes a disease. ^{7, 8, 9} In Duchenne, gene therapy aims to slow or stop disease progression, helping people keep muscle function for longer. ^{10, 11}

Gene therapies can work in several ways, including:

• Replacing a mutated gene with a healthy variant.
• Silencing or inactivating a gene that is not functioning correctly.
• Adding a new or modified gene that helps counteract the disease. ^{8, 9}

Types of Gene Therapy for Duchenne

There are two main kinds of gene therapy that scientists are investigating to help treat Duchenne:

Gene Replacement for Duchenne

In Duchenne, gene replacement works by delivering a healthy, artificial (exogenous) gene into the muscle cells. The goal is to replace the faulty gene that causes the disease.¹⁰

This approach normally uses a carrier (called a vector) to transport the gene into the cells. This carrier is usually an inactive virus that has been modified in the lab, so it is unlikely to cause infection. Because viruses naturally know how to enter cells and deliver genetic material, they can be adapted to carry therapeutic genes to the tissues where they are needed. ¹² The most common one used is called Adeno-Associated Virus (AAV). ^{13, 14, 15}

Even though this approach is generally considered quite safe, it can still have some risks.  Some people may have reactions from their immune system (which can recognize the viral vector, attack it and neutralize it) or experience side effects such as liver problems, nerve damage, or other complications. ^{16, 17}

AAV vectors can only carry small pieces of genetic material, so the full dystrophin gene is too large to fit. To solve this, researchers created shorter versions of the gene, called mini-dystrophin and micro-dystrophin. These smaller genes still perform the most important functions of dystrophin but are small enough to fit inside the AAV.¹⁵

Once inside the muscle cells, these modified genes give the body the instructions it needs to make a working form of dystrophin. ^{10, 15} This method could possibly be relevant for people with different Duchenne mutations, although more research is needed. ¹⁵

Current Use of Gene Replacement Therapy for Duchenne

At the time of writing, Elevidys (delandistrogene moxeparvovec-rokl) is the only approved gene therapy for Duchenne Muscular Dystrophy (DMD) in some parts of the world, including: ^{10, 18}

United States

Elevidys was initially approved in 2023 through accelerated approval
(which allows earlier access while more studies are conducted to further investigate the potential risks and benefit) for the treatment of children aged 4 through 5 years old with Duchenne who can walk.

In 2024, Elevydis received full and traditional approval for children aged 4 years and older who can walk.

Elevidys was also made available for children with Duchenne aged 4 and older who cannot walk through the FDA’s accelerated approval pathway. ^{18, 19, 20} However, this approval was paused after two people experienced fatal liver failure after receiving the treatment. ^{21, 22, 23} Following a careful review of these events, the FDA has updated the prescribing information, and Elevidys is no longer approved for children who cannot walk.

Japan

Elevidys was approved in June 2025 by the Ministry of Health, Labour, and Welfare (MHLW) for children aged 3 to under 8 years who can still walk. ^{24, 25}

Other countries

By June 2024, Elevidys was already approved for use in Qatar, Kuwait, the UAE, Oman, and Bahrain. In January 2025, it was also announced that Brazil and Israel had approved Elevidys for children with Duchenne who can still walk and are between 4 and 7 years old. Approval details vary by country and depend on local regulations. ^{21, 26}

In these countries, Elevidys  is currently available for children with Duchenne who can walk, provided they meet other medical requirements that have been set specifically in each country.

In Europe, the European Medicines Agency (EMA) has reviewed Elevidys but has not granted approval. This means the treatment is not available as part of regular care in European countries. ^{27, 28, 29}

Ongoing Research in Gene Replacement Therapies for Duchenne

Other gene replacement therapies are being tested in clinical trials. All of them use a shortened, engineered version of the  DMD gene that produces a smaller dystrophin protein called micro-dystrophin.

These therapies are still in the research stage and are not part of standard medical care. The only way to access them is by joining approved clinical trials that test their safety and effectiveness. The approaches differ in several ways, including:

• The type of Adeno-Associated Virus (AAV) used to carry the gene.
• How the shortened dystrophin gene is built. For example, which parts of the original gene are kept or removed.
• The medicines used to help control the immune system’s response.

These trials are at different stages of testing and may focus on different groups of people. ^{30, 31, 32, 33, 34, 35, 36, 37}

Gene Editing for Duchenne

This technique involves targeting the specific change in the DNA sequence that causes the disease and modifying it, with the aim of permanently correcting it.

Although there are different methods of gene editing, the most studied for Duchenne is the CRISPR-Cas system. ^{38, 39, 40}

This gene editing system works in some basic steps:

• A guide molecule or ‘template’ that directs the system to a specific location in the DNA, such as the site of a genetic mutation.
• A special protein acts like scissors and cuts the DNA at that spot.
• The cell then tries to fix the cut using its natural repair system.
• During this repair, the faulty DNA in the dystrophin gene may be removed, fix or replaced with a working copy.^{38, 39, 40}

Gene editing is a mutation-specific approach, meaning it can only treat cases of Duchenne that involve the particular mutation it is designed to target. ^{38, 39, 40}

Currently, there is one Duchenne clinical trial taking place in China that is using this technique. Other studies are still being done in laboratories before they can move to human trials. ⁴¹

How Long Does It Take for New Investigational Therapies to Get Approved?

Developing and approving a new investigational treatment takes many steps and a lot of time. On average, it takes about 10 to 15 years from first finding a possible drug to getting it approved for patients. ^{42, 43} This includes:

Drug Discovery and Preclinical Testing

In this early stage, scientists identify or design a potential new drug. Before it can be tested in people, it is first tested in labs and in animals. These first tests help check its safety and whether it might work as intended. ^{42, 44} This phase typically takes around 6.5 years.⁴³

Clinical Trials: Phases, Timelines, and What They Involve

If early testing is successful, the drug can move into human studies. These studies are also called clinical trials. In these studies, investigational treatments are tested in volunteers.

On average, it takes about 7.3 years from the start of the first human trial to full approval. ⁴⁵ These trials are conducted in three main phases:

• Phase I: A small group of volunteers receive the drug to evaluate safety, dosage, and how the body responds. Volunteers may be healthy individuals or people with the condition.^{42, 44} This phase typically lasts from several months to 2 years. ^{44, 46}
• Phase 2: The drug is tested in a larger group of people with the condition. This helps assess how well the drug works for a larger population and to monitor for side effects.^{42, 44} This phase normally takes from several months to 2 years. ^{43, 44}
• Phase 3: The phase aims to confirm how well the drug works and compare it to existing treatments or a placebo. A placebo is a substance or procedure that looks like the real treatment but doesn’t contain any medicine. It may be an inactive pill, injection, or similar intervention. Phase 3 trials also help identify rare side effects. [42], [44] This phase usually lasts from 1 to 4 years. ^{43, 44, 47}

In many diseases, Phase 2 and Phase 3 trials may include several hundred or even thousands of participants. But in rare conditions like Duchenne, trials often include fewer people because there are fewer eligible patients. ^{48, 49}

Drug Regulatory Review and Approval

Typically, once all trial data is collected, the research team submits the results to regulatory agencies. However, in certain situations submission can occur earlier, once sufficient clinical data are available. These agencies, such as the Food and Drug Administration (FDA) in the United States or the European Medicines Agency (EMA) in Europe, review the evidence in detail and may approve the treatment if its benefits outweigh the risks. On average, this review process takes about 1.5 years.^{43, 47}

What Factors Can Affect Drug Approval Timelines?

The time needed for drug approval can vary. Several factors can affect how long it takes, including:

• Similar drugs are already approved: The approval process may be faster if the new therapy is closely related to an already approved treatment. ⁴⁴
• Urgent medical need: Some therapies developed for serious or life-threatening conditions may qualify for faster review pathways. This includes diseases with few or no treatment options, such as Duchenne. ^{44, 46}

Faster review programs include Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval, all of which can shorten approval timelines. These pathways were updated under the Food and Drug Administration Safety and Innovation Act (FDASIA), a law passed by the U.S. Congress in 2012. ²⁹

• Clear benefit over current treatments: If early studies show the new investigational drug works significantly better than current treatments, the review process may be faster. ^{44, 46}
• Type of product: Some treatments, such as gene or cell therapies, cause complex changes to cells. Because of this, they often require more review time than treatments that involve only small changes.⁴⁶

Phase 4 Studies and Ongoing Safety Monitoring

Monitoring continues even after a drug is approved. After approval, it enters Phase 4 trials, also called post-marketing safety studies. These studies often include thousands of people with the condition the drug is intended to treat.

Phase 4 studies help show how well the drug works in everyday life and what side effects may appear. If new safety issues are found, the guidance for using the drug may be updated. If serious safety problems keep appearing, the drug may be removed from the market.^{43, 44}

Conclusions

Duchenne Muscular Dystrophy (DMD) is caused by mutations in the DMD gene. These mutations prevent the body from producing functional dystrophin, a protein that helps keep muscles strong and working properly.

Gene therapy aims to fix these mutations through two main strategies: gene replacement  and gene editing.

• Gene replacement uses an often-harmless virus, typically adeno-associated virus (AAV), to deliver a shortened version of the DMD gene that can produce a functional, although smaller, form of dystrophin in muscle cells
• Gene editing directly modifies DNA to correct mutations. The most studied gene editing method is called CRISPR-Cas.

It generally takes about seven years from clinical trial initiation to full regulatory approval. Because gene therapies change how cells work, they often face stricter rules and longer review times.

Elevidys, a gene replacement therapy delivered through an AVV-based gene delivery approach, is currently the only approved gene therapy for Duchenne in some countries. However, other gene therapies are being studied in clinical trials or earlier studies.

At myTomorrows, we have a team of Patient Navigators, who are multi-lingual professionals with a medical background, who can help you to explore your treatment options and support you through your journey.

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