Gene therapy is an emerging approach for treating Duchenne muscular dystrophy (DMD). It works by restoring or modifying genes to help the body produce proteins essential for muscle function and repair. One promising gene-editing tool is CRISPR, which stands for “clustered regularly interspaced short palindromic repeats.” This technology allows scientists to precisely modify DNA.

While CRISPR-based treatments are not yet approved for DMD, researchers are studying this technology for its potential to correct genetic mutations (changes) that cause the disease.

If you or a loved one is interested in learning more about gene therapy for DMD, this article will cover key details to help you stay informed about this developing field.

1. CRISPR Is a Promising Gene-Editing Technology

Gene editing is a process that changes or repairs DNA sequences. CRISPR is a gene-editing tool that allows scientists to target and modify specific sections of DNA. You can think of it like a “find and replace” function in a document — except instead of words, researchers identify faulty genetic sequences and attempt to correct them.

In DMD, mutations in the DMD gene prevent the body from making a working version of dystrophin, a protein essential for muscle strength and protection. Without dystrophin, muscle cells weaken and become damaged over time, leading to progressive muscle loss and the symptoms of DMD.

2. CRISPR Technology Was Discovered in Bacteria

Scientists first discovered CRISPR technology while studying bacteria. In nature, bacteria use CRISPR as a defense system against viruses. When a virus attacks, bacteria store a small piece of the virus’s DNA, allowing them to recognize and fight future infections.

A key part of this system is a protein called CRISPR-associated protein 9 (Cas9). Cas9 acts like molecular scissors, cutting DNA at specific locations. Researchers have learned how to guide Cas9 to target and edit specific genes, which may allow them to correct mutations that cause diseases like DMD.

3. There Are Four Main Techniques Used for CRISPR Therapy

Researchers are exploring different CRISPR-based strategies to restore dystrophin production in muscle cells, which could potentially slow disease progression in Duchenne muscular dystrophy. Following are four key techniques being studied.

Exon Skipping

Exon-skipping therapy is a gene-editing approach that allows cells to “skip over” faulty sections of the DMD gene called exons. Exons contain instructions for making proteins, including dystrophin. In some cases of DMD, mutations disrupt these instructions, preventing the body from making functional dystrophin.

By skipping faulty exons, CRISPR may allow the dystrophin gene to produce a shorter but partially functional version of dystrophin. While not identical to the full-length protein, this shorter version may help protect muscle cells and slow disease progression. This may reduce DMD symptoms and make them more similar to those of Becker muscular dystrophy (BMD). BMD is a milder form of the disease that causes muscle weakness, particularly in the hips and legs.

Exon Reframing

Exon reframing is a gene-editing strategy that aims to correct mutations by adding or deleting small DNA segments. This process reframes the dystrophin gene so that cells can read its instructions correctly and make a functional version of the protein.

Compared to exon skipping, exon reframing could potentially correct a broader range of DMD mutations while preserving more of the dystrophin gene’s original structure.

Exon Knock-In

Exon knock-in therapy aims to restore missing sections of the DMD gene by inserting functional exons. This gene-editing approach “knocks in” the missing genetic material, potentially allowing the body to produce a fully functional dystrophin protein. While early preclinical studies have shown promise, more research is needed before this method can be tested in humans.

Base Editing

Base editing targets and fixes single-letter (point) mutations in DNA without cutting the DNA strand. By directly changing a single DNA base, this technique may correct certain mutations that prevent the body from making functional dystrophin.

Researchers are also studying a related technique called prime editing, which could potentially fix a broader range of genetic errors.

CRISPR-based therapies offer a potential way to target the root cause of DMD rather than just treating symptoms. By focusing on specific genetic mutations, researchers hope to develop long-term, personalized treatment options for people living with DMD.

4. Viruses Can Be Used To Deliver CRISPR Treatment

CRISPR treatment can be delivered with or without viruses. The most common viral method is called adeno-associated virus (AAV) gene therapy. While the word “virus” might sound concerning, these viruses are modified to be safe — scientists remove harmful genes and instead use the virus as a carrier for helpful genetic material.

If viruses aren’t used, scientists may deliver CRISPR treatment using small particles called lipid nanoparticles. The particles are designed to enter cells like viruses. However, AAV is usually preferred because it does a better job of reaching specific muscle tissues.

5. There Are Risks Associated With CRISPR Therapy

Gene therapy using AAV vectors is generally considered safe for CRISPR treatment. However, there are possible risks. High doses of AAV may cause side effects like nausea and vomiting. Rare side effects have been reported, including liver damage, heart muscle inflammation, kidney failure, and life-threatening complications or infections.

6. CRISPR Technology for DMD Is Promising

Researchers are hopeful that CRISPR technology may one day provide a permanent way to correct mutations in the dystrophin gene. Studies suggest that restoring dystrophin through gene therapy can help slow the progression of DMD. In some cases, it may even help improve muscle strength.

Other types of gene therapies for DMD use similar strategies as CRISPR. For example, exon-skipping drugs that don’t use CRISPR technology are already approved for some people with DMD.

CRISPR-based gene-editing treatments are mostly in the preclinical phase, where they are tested in animals and lab-grown tissue samples. However, some have advanced to early-stage clinical trials in humans. Researchers have also developed a specialized DMD mouse model to study CRISPR treatments, and research exploring CRISPR technology in humans with DMD is ongoing.

CRISPR-based gene therapies require specific scientific protocols to ensure the benefits outweigh the risks. Participants in trials are screened to identify specific mutations in their dystrophin gene. Once treatment is prepared, healthcare providers administer the therapy and closely monitor participants for any reactions. Researchers also adjust dosages to determine the safest and most effective approach.

7. Research Is Key To Making Advances in DMD Treatment

CRISPR gene therapy for DMD is still in its early research stage, but progress is happening quickly. Scientists continue to study gene therapy for DMD to ensure it is both safe and effective.

In 2023, the U.S. Food and Drug Administration (FDA) approved exagamglogene autotemcel (Casgevy) as the first CRISPR-based gene therapy. This treatment is approved for certain blood conditions, including sickle cell disease and beta thalassemia. Other CRISPR-based treatments are currently in clinical trials for people with a variety of health conditions, including:

• Urinary tract infections
• Hereditary transthyretin amyloidosis
• Hereditary angioedema
• Cancer

DMD researchers hope to build on the success of CRISPR in other genetic disorders. If you’re interested in learning more, talk to your healthcare team about ongoing and future clinical trials for CRISPR-based treatments in DMD.

Connect With Others Who Understand

On myMDteam, the site for people with muscular dystrophy and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with muscular dystrophy.

Have you or a loved one undergone gene therapy for DMD? What has your experience been like? Share your experiences in the comments below or on your Activities page.