Research and Clinical trials

Muscular Dystrophy is caused by genetic mutations resulting in absence or malformed protein. A variety of genetic mutations are implicated in muscular dystrophies and display a broad range of symptoms.

A number of therapies are in development as present which aim to insert a replacement gene or correct the mutation. These therapies are relatively new and while incredibly promising require thorough research and trials before they become commercially available.

Summarised below are a number of these therapies and how they address correction of Muscular Dystrophy causing mutations:

Gene replacement therapy

Gene therapy has the potential for directly addressing the primary cause of Muscular Dystrophy by providing for the production of the missing protein. Challenges to be overcome include determining the timing of the therapy (to possibly overcome the genetic defect), avoiding or easing potential immune responses to the replacement gene, and, in the case of Duchenne Muscular Dystrophy, the large size of the gene to be replaced.

For those MDs with central nervous system (brain) consequences (congenital muscular dystrophy and myotonic dystrophy), researchers are developing and fine-tuning gene therapy vectors (a way to deliver genetic materials to cells) that can cross the protective blood-brain barrier.

Genetic modification therapy to bypass inherited mutations

Many individuals with Muscular Dystrophies have mutations in the affected gene that cause it to function improperly and stop producing the correct protein. By modifying the protein production process, there is potential to produce a gene where the mutation is skipped to produce a partially functional protein. 

Two strategies are currently under study to bypass dystrophin mutations, one of which is  drugs that cause the protein synthesis machinery to ignore the premature stop signal and produce functional dystrophin. This strategy, which is potentially useful in about 15 percent of individuals with Duchenne Muscular Dystrophy, is currently in clinical trials. Second, a more recent approach uses antisense oligonucleotides (short strands of nucleic acid designed to block the transfer of some genetic information into protein production) to alter splicing and produce nearly a full-length dystrophin gene, potentially converting an individual with Duchenne to a much milder Becker Muscular Dystrophy.

Drug-based therapy to delay muscle wasting by promoting muscle growth

Progressive loss of muscle mass is primarily responsible for reduced quality and length of life in Muscular Dystrophy. Drug treatment strategies designed to slow this muscle degeneration can have substantial impact on quality of life. These can include the following:

  • Glucocorticoids such as prednisone or deflazacort, which was approved by the U.S. Food and Drug Administration (FDA) for treating DMD in 2017. Studies show that daily treatment with prednisone can increase muscle strength and respiratory function and slow the progression of weakness in MD.
    • A new glucocorticoid treatment called vamorolone is being studied in boys with DMD. Early results showed the treatment had similar benefits to those from prednisone but without the side effects.
    • NICHD-funded researchers found that vamorolone also helped treat symptoms of limb-girdle MD in animal models. (PMID 30166241)
  • Anticonvulsants. Typically taken for epilepsy, these drugs may help control seizures and some muscle spasms in people with MD.
  • Immunosuppressants. Commonly given to treat autoimmune diseases such as lupus and eczema, immunosuppressant drugs may help delay some damage to dying muscle cells in MD.
  • Beta blockers, angiotensin-converting-enzyme (ACE) inhibitors, and other medications for treating heart problems, such as high blood pressure and heart failure, which are associated with certain types of MD.

Similarly, skeletal muscle has the ability to repair itself, but its regeneration and repair mechanisms are progressively depleted during the course of several types of Muscular Dystrophy. Understanding the repair mechanisms may provide new therapies to slow, and possibly stabilise, muscle degeneration.

Cell-based therapy

The muscle cells of people with Muscular Dystrophy often lack a critical protein, such as dystrophin in Duchenne MD or sarcoglycan in some of the limb-girdle Muscular Dystrophies.

Scientists are exploring the possibility that the missing protein can be replaced by introducing muscle stem cells capable of making the missing protein in new muscle cells. Such new cells would be protected from the progressive degeneration characteristic of MD and potentially restore muscle function in affected persons.