Gene therapy offers hope for treating a wide range of inherited and acquired diseases and conditions, ranging from muscular dystrophy to obesity. Gene therapy for muscular dystrophy research reached a milestone recently: in June of 2023, the FDA made Elevidys the first FDA-approved gene therapy for Duchenne muscular dystrophy (DMD) in pediatric patients. Elevidys is part of a select group of just over 30 gene therapies that are currently FDA-approved. While gene therapies for obesity are not yet on that list, researchers hope that will someday change. As gene therapy technology continues to improve, expand, and evolve, researchers hope this will lead to better treatment outcomes for more patients.
Gene Therapy for Muscular Dystrophy: Recent Milestones
Muscular dystrophy is a disorder caused by mutations in genes that encode proteins critical for muscle function. There are 30 different types of muscular dystrophy, but all involve some degree of progressive weakness in the muscles that control movement. Some forms of the disease may cause mild symptoms that progress slowly and have minimal impact on daily functioning, while others are severe, causing rapid muscle wasting, physical disability, and (in some cases) a shortened lifespan. The severity of symptoms a patient experiences can vary widely, depending on the type of muscular dystrophy, the rate of disease progression, the muscles affected, and the age of diagnosis.
To date, there is no cure for muscular dystrophy. Treatments are primarily focused on managing symptoms and slowing muscle atrophy where possible. However, in recent years, gene therapy for muscular dystrophy has emerged as a potentially groundbreaking new way to treat certain forms of the disease.
Gene Therapy for Duchenne Muscular Dystrophy (DMD)
Duchenne muscular dystrophy (DMD), one of the two most common forms of muscular dystrophy, typically appears during early childhood. DMD progresses rapidly, causing deterioration of both skeletal and heart muscles. Most children with the condition lose the ability to walk by the age of 12, and the majority will eventually require a respirator to breathe.
DMD is caused by a defective gene for dystrophin, a protein needed for muscle strength. DMD remains a particular area of focus in gene therapy for muscular dystrophy research. Not only are muscle cells considered an ideal target for gene therapies, but the monogenicity of DMD, in particular, makes it amenable to gene transfer therapy (which focuses on replacing a single gene).
Gene therapy for DMD focuses on spurring the production of a micro-dystrophin protein, a shortened (but still functional) version of dystrophin. Gene therapy cannot cure DMD or restore lost muscle cells, but it has enormous promise as a treatment that can help stabilize and slow symptom progression.
One of the first breakthroughs in gene therapy for muscular dystrophy research came in June 2023, when the FDA approved Elevidys, the first gene therapy treatment approved for treating DMD in pediatric patients between the ages of four and five. Elevidys utilizes recombinant gene therapy, a unique treatment approach that uses a single infusion of genetically modified viruses carrying a gene that produces a miniature version of dystrophin, a muscle-protecting protein.
Gene Therapy for Obesity
Obesity is a complex disease that can be driven and influenced by a combination of genetic and environmental factors. Obesity and related metabolic disorders are considered a global health concern. Gene therapies for obesity are at the forefront of new methods for treating this complicated, multifaceted disease.
In May 2023, researchers from the University of Barcelona published a study showing preclinical success using gene therapy to combat obesity and diabetes in mouse models. The team’s strategy, which used an ex vivo gene therapy technique, involved generating and implanting cells expressing the CPT1AM protein, an enzyme that plays an essential role in metabolic diseases like obesity. The team demonstrated that CPT1AM gene therapy reversed diabetic and obese phenotypes in the mouse models, resulting in lower body weight, reduced hepatic steatosis, lower insulin and cholesterol levels, and improved glucose tolerance. The treated mice also showed reduced adipose tissue-related issues and improved cellular health.
More research is needed before this approach is ready for human trials. Laura Herrero, the study’s lead author, notes, “To approximate the therapy in humans, we need to optimize several processes such as the quality and viability of stem cells from adipose tissue isolated from people with obesity, the percentage of infection with lentivirus, and the number of cells used for transplantation.”
However, Herrero and her team believe their results strongly support the potential future clinical use of this gene therapy strategy to reduce obesity and cholesterol rates in the population.
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Gene therapies may be the key to providing treatments and cures for various genetic and acquired conditions. Researchers are already exploring how gene therapy might help the fields of oncology and ophthalmology as well as those suffering from blood cancer, leukemia, and sickle cell disease. One day, they may offer viable options to treat and even cure diseases once considered incurable.
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