Tragic Outcome in DMD Gene Therapy

A 16-year-old patient with Duchenne muscular dystrophy (DMD) died from acute liver failure after being treated with Sarepta Therapeutics' gene therapy, Elevidys®. This therapy aims to deliver a functional version of the dystrophin gene, which is mutated in DMD patients, using a viral vector. This approach seeks to enable dystrophin protein production, which is crucial for muscle function, potentially slowing or halting the disease's progression. This incident marks a severe case of liver injury not previously reported with this therapy. Sarepta has stated that while the treatment has a positive benefit-risk balance, it will update its prescribing information. The liver failure could have been exacerbated by a recent cytomegalovirus infection the patient had, which can damage the liver. This event has prompted discussions about gene therapies' unpredictability and investment risks.

Gene therapies offer transformative potential in treating various genetic disorders by introducing, removing, or altering genetic material within a patient's cells. These therapies can potentially correct or replace malfunctioning genes responsible for disease, offering treatments for conditions that were previously considered untreatable. By directly addressing the genetic root of a disease, gene therapies can reduce symptoms, halt disease progression, and in some cases, potentially cure the condition. This represents a significant advancement in personalized medicine, tailoring treatments to individual genetic profiles. Although it is important to take each patient's death seriously, I believe that this should not stop the use of gene therapy because of how much more the medical field still needs to learn about our genome. Using specific genes, medicine can target mutations very specifically and lead to a world without problematic genetic disorders.

Links:

https://www.genengnews.com/topics/genome-editing/dmd-patient-dies-after-treatment-with-sarepta-gene-therapy/

https://www.mayoclinic.org/tests-procedures/gene-therapy/about/pac-20384619

Dogs with muscular dystrophy receive CRISPR treatment

Dogs with Duchenne muscular dystrophy (DMD) were treated with the CRISPR genome editor to restore production of the missing protein responsible for the disease. The dogs showed obvious signs of behavioral improvement such as running and jumping. DMD is an x-linked genetic disorder that affects about 1/3600 boys worldwide. Progressive muscle degeneration and weakening can begin as early as 3 years old and affect every muscle in the body, eventually leading to life threatening complications from heart and respiratory muscle weakness. This study used DMD beagles with a genetic mutation similar to the most common mutation in humans, making it an important model for the clinical translation of CRISPR gene editing

In this study, four 1-month-old beagles were treated with dystrophin-targeted CRISPR either directly in a leg muscle (2 dogs) or intravenously at either a low or high dose (the other 2 dogs). Six weeks after muscle injection, the dogs’ leg muscle was making dystrophin at about 60% of healthy levels, compared to almost none pre-treatment. After 8 weeks, the dog treated intravenously with a high dose made dystrophin at 5-92% of healthy levels in various muscles, notably 92% in the heart and an average of 50% restoration in three leg muscles. Long-term studies with more dogs are needed for verification before even considering clinical trials.

Promise in Tackling Muscular Dystrophy

Muscular Dystrophy, is “when damaged muscle tissue is replaced with fibrous, fatty or bony tissue and loses function”¹ has impacted around 250,000 people in the United States, and Duchenne Muscular Dystrophy (DMD) only affects boys. Recent clinical studies have been conducted on dogs to treat DMD during the early stages of development, and human trials are scheduled to begin in the next few years.

                                                                                  

Boys with DMD have a mutation in their genes that interrupt dystrophin protein production, and thus cause a phenotypic complication. The muscle cells degenerate, resulting in difficulty in mobility, such as walking and even breathing. Gene therapy has been unsuccessful in the past due to the large size of the gene, however past research has allowed the development of a microgene, in which a gene therapy vector can carry a micro-dystrophin to all muscles by way of a virus to offer protection of this disease.

This brings hope to boys who are showing early signs of Duchenne Muscular Dystrophy. With this microgene, there is promise for their muscle cells to be protected from this disease, as well as prevent further degeneration of mobility. This will be the beginning of these boys taking their life back, and truly living to the fullest.

Sources:

1. https://www.sciencedaily.com/releases/2015/10/151022141722.htm

2. http://munews.missouri.edu/news-releases/2015/1022-gene-therapy-treats-all-muscles-in-the-body-in-muscular-dystrophy-dogs-human-clinical-trials-are-next-step/