Will Gene Therapy Be the Next Cure for Duchenne Muscular Dystrophy?

By: Khushi Sheth


Image Credit: Flickr @ 1Droid JamLos

Muscular Dystrophy (MD) is a disease characterized by significant muscle weakness that can greatly affect a person’s daily functioning. MD is caused by mutations in genes that code for muscle proteins, which affect their development. The severity of symptoms ranges from moderate to severe muscle weakness in different parts of the body, with some patients with muscular dystrophy surviving only into their teenage years. Muscular Dystrophy is the umbrella term for what are many different types of MD that affect different parts of the body and have very different health outcomes. The focus of this blog is a type of MD called Duchenne Muscular Dystrophy (DMD), one that mainly affects a person’s limbs. DMD is a recessive trait caused by a mutation on the X-linked gene. Because the gene associated with DMD is found only on the X-chromosome, males, with XY chromosomes, are more likely to contract the disease from their mothers than females, with XX chromosomes. If a person with XX chromosomes contracts DMD, they would have inherited two copies of the mutation, one from both parents, whereas a person with XY chromosomes would have inherited one copy of the mutation. When this happens, it is because the person inherits one copy of the DMD mutation from each parent.

The specific mutation associated with Duchenne Muscular Dystrophy occurs in a protein called dystrophin, and without this protein, muscle cells can be easily damaged. The dystrophin protein causes muscle contraction inside the muscle cell outward to the cell membrane. One end of the dystrophin protein is responsible for linking the proteins inside the muscle cell interior and the other end links various proteins to the cell membrane. Because the dystrophin protein is so long, there is usually a mutation in the gene encoding for the middle portion of the protein, called the spectrin repeats. When the mutation occurs, the whole protein stops functioning. Since dystrophin plays such an important role in muscle contraction, the muscle cells cannot function properly, which results in fibrous tissue forming in the muscle called inflammation. The combination of the increasing inflammation to the body’s immune system and disruptions in the function of scaffold proteins can cause severe muscle damage and progressive weakness. Such deformations usually begin in infancy.

Gene therapy is a relatively new form of medical care that alters a person’s DNA with technologies like molecules that silence genes or drugs that “skip” portions of a gene (called an exon). Gene replacement therapy targets the root cause of genetic illnesses by delivering a healthy gene to replace the flawed one, making it an excellent option for treating DMD. Researchers hope to insert the Dystrophin gene in the patients’ DNA by injecting the healthy gene into a harmless virus and exposing the patient with the virus. Since the primary function of a virus is to replicate its own genetic material inside a host, the virus will be able to insert the healthy gene into the patient and replicate a smaller version of the Dystrophin protein.

While this is a promising new treatment, there are several limitations to this approach. One challenge is that the dystrophin protein is very large. Since not all engineered viruses can hold the large size of the Dystrophin gene, researchers have developed a smaller version of the dystrophin gene to inject into the virus. Viruses also spread throughout the host very quickly and researchers don’t want the presence of the new protein in the body to trigger an immune response. Some trials have proved to be ineffective as patients have experienced an immune response to the gene and the large protein it codes for. But even smaller versions of the gene are currently in the process of being developed. To address how these genes are going to reach the muscle cells and not other cells in the body, researchers have also created a muscle-specific promoter that acts like a control switch for the dystrophin gene. Muscle-specific promoters activate the gene in the muscle tissues and remain dormant in other tissues to prevent any severe side effects.



Educational Content


Q: What is the life expectancy for people born with muscular dystrophy?

A: Most males with muscular dystrophy live normally with mild symptoms while others experience severe muscle weakness, dying in their teenage years.


Q: How is Duchenne Muscular Dystrophy different from other types of Muscular Dystrophy?

A: Duchenne Muscular Dystrophy mainly impacts the limbs. Becker Muscular Dystrophy is a more form of Duchenne Muscular Dystrophy while Myotonic Muscular Dystrophy only occurs in adults contrary to Duchenne Muscular Dystrophy.


Q: Is it possible for a female to have Duchenne Muscular Dystrophy?

A: Yes, in the rare case that a female has Duchenne Muscular Dystrophy, she would have inherited the X-linked gene for Muscular Dystrophy from both parents. The father would have had muscular dystrophy already and the mother would’ve been a carrier.


Citations

  1. https://www.mda.org/disease/duchenne-muscular-dystrophy

  2. https://www.mda.org/disease/duchenne-muscular-dystrophy/causes-inheritance

  3. https://www.cdc.gov/ncbddd/musculardystrophy/facts.html

  4. https://www.mda.org/disease/duchenne-muscular-dystrophy/research

Image Credit:

No changes were made to the following image: https://www.flickr.com/photos/jamlos/2734418031/in/photolist-5aCBdt-5fbtnc-fPYWNV-fPYY58-fPYXwk-fPYXca-fPYXS8-fQgw2o-24ChYcg-fPYXUz-fPYXb2-fQgwcJ-fPYXrF-fPYX6M-fPYXvc-fPYXj8-fQgw8j-fPYWJD-fQgvwS-fPYYm6-fQguS9-fQgvXq-fPYXYe-fPYXxZ-fPYWZp-fQgw15-fPYXEe-fQgvJw-fQgv3C-fPYY4M-fQgw1C-fPYXF4-fQgw9h-24CdQpk-WVyFgm-24CdQiD-6LxArf-fPYXRt-fPYXZn-fPYXPB-fQgwaC-fPYXra-fQgw69-fQgvZq-fQgvAS-fPYY3Z-fQgvH9-fPYXR4-fPYXsr-fQgv1w

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