Developing ways of regenerating skeletal muscle is becoming incredible important as more than 30 muscular dystrophies and more than 100 muscle diseases have been identified¹². This is in addition to the general loss of muscle strength and function associated with age. Given the diversity of diseases, it would take more than just a single therapy to regain function in all potential patients, but one successful treatment could benefit a large number of patients and serve as a building block to additional therapies.

Muscular Dystrophy

Given that there are more than 30 different muscular dystrophies, the term is a very broad one. In general, "muscular dystrophy is a phenotype produced by many different genetic mutations, is characterized by progressive muscle weakness and degeneration with cycles of muscle necrosis and regeneration"¹².

Specific Examples of Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD): DMD is the most common muscular dystrophy, affecting 1 out of 3,500 boys, as well as the most well understood muscular dystrophy. Almost all affected boys show symptoms by 5 years of age, including lower body muscle weakness⁷. The progression of the disease leaves the individuals wheelchair-bound by their teens, and death occurs in the twenties due to respiratory and cardiovascular failure¹². DMD occurs because of a genetic defect in the dystrophin gene. Dystrophin is the largest gene in the human genome at 2.5 Mb in 79 exons, coding for a 427 kDa protein, and is found on the small arm of the X chromosome¹⁰ Dystrophin is a central element of a multiprotein complex that provides stability to the muscle cell membrane during contraction⁹. Mutations with in dystrophin result in a fragile cell membrane, so affected muscle cells die earlier and more often as they are often under strain from muscle contractions. Large scale deletions and duplications account for 60 percent of DMD cases, with point mutations accounting for as much as 40 percent of DMD patients⁸. Approximately one third of DMD cases are due to novel mutations, making a routine prenatal diagnostic test extremely difficult. This high rate of novel mutations also means that the demand for treatments is likely to remain constant in the future¹⁰. There is no curative treatment currently for DMD or any of the muscular dystrophies. The standard treatment for DMD is glucocorticoids, a steroid molecule that has been shown to slow the decline of muscle strength, allow the patient to retain the ability to walk for longer, and slow respiration loss¹⁰. Other treatments have been proposed through animal studies, but none have shown improved outcomes in large clinical trials.
Becker Muscular Dystrophy (BMD): BMD is also the result of a genetic defect in the dystrophin gene, but has a milder phenotype because the dystrophin protein is often partially functional¹².

Congenital Muscular Dystrophies (CMD): CMD are a group of muscular dystrophies that are autosomal recessively inherited. They present at birth as a "floppy infant lacking muscle tone"⁸. Though not always, non-muscle problems are common with CMD, such as various neurological issues. The mutations associated with CMD are usually in genes that code for enzymes that perform a certain type of glycosylation (adding a sugar to a protein). This type of glycosylation is rarer than others, but one major protein affected is dystroglycan, another protein in that same protein complex with dystrophin that provides stability to the muscle cell membrane⁸.