Scientists and doctors have been working for many years on developing and testing a variety of strategies for treating Duchenne and Becker muscular dystrophy.
While some strategies are aimed at correcting the root cause, other methods are aimed at reducing the symptoms.
Research Approaches to Addressing Duchenne
Strategies Addressing the Root Causes
Treatments in this category aim to correct the root problem in Duchenne, a mutation in the dystrophin gene.
Exon skipping and nonsense mutations (also known as stop-codon read through) drugs have been designed to help people with specific mutations produce a functional version of the dystrophin protein and have been under investigation in humans for many years. In the case of exon skipping, some treatments have already been approved, and others are in the pipeline.
Another promising area of research is gene editing (CRISPR/Cas9) which has the potential to be used to correct specific mutations, although the testing for this strategy is still pre-clinical.
Gene therapy is another promising potential therapeutic that is in the clinical trial stage of investigation. The idea is to deliver a copy of the dystrophin gene to muscle cells using a virus. The virus has all the components that negatively affect cells removed and instead contains the instructions for making the protein. Since the dystrophin protein is so large, it cannot all fit into a virus because most viruses contain much less DNA than the gene. The genes that are delivered have been altered to contain the most important segments of DNA. The goal is to make the most functional version of the protein, despite being much smaller than the actual gene. Currently, there are different biotech companies testing gene therapies, each with a slightly different form of the shortened dystrophin gene.
Strategies Addressing the Symptoms of Duchenne
The lack of dystrophin in Duchenne patients leads to a constant breakdown of muscle. There are many different potential therapeutics that are currently under investigation, which all work to protect muscle or stimulate muscle growth. This is a very broad category of approaches, all having very different mechanisms, but a similar goal. These do not target the root cause but can still have a very beneficial effect in reducing the symptoms of the disease.
One of the results of the constant breakdown of muscle is inflammation. While inflammation is an integral part of the immune system, it is meant to be short-term. Long-term inflammation has a negative impact on the muscle. Thus, reducing inflammation can have a protective result on the muscle tissue.
Corticosteroids are one of the most well-known examples of an anti-inflammatory medication. Currently, most Duchenne patients are on corticosteroids. Deflazacort and Prednisone are the most common steroids used. Currently, alternative corticosteroid treatments like varmorolone are being tested. These potential therapeutics aim to have the same ability to reduce inflammation with fewer side effects.
Eliminating scar tissue and fibrosis is an important strategy in Duchenne. As the muscles break down and become damaged, the cells are replaced with scar tissue and fat in a process called fibrosis. Fibrosis interferes with the structure and strength of the muscles in Duchenne patients. Anti-fibrotic therapy could be a very useful strategy, as it may reduce scar tissue formation and improve muscle structure and function.
Consistent muscle damage also wears down the outer protective layer of the muscle. The outer layer is important for controlling what comes into and goes out of the muscle. One of the most important roles of this layer is to ensure different minerals remain in the right proportions on either side of this muscle layer. These minerals, which include sodium, potassium, and calcium, are necessary for powering the contractions of the muscular layers. However, when the outer layer of the muscle is damaged, these minerals leak into the cells and build up in inequal proportions, effecting the muscles’ ability to generate power and contract. A treatment strategy that can restore the balance of minerals leaking into the cells would be very beneficial and could improve muscle contraction.
The mitochondria, known as the “powerhouse of the cell,” are also very important in generating power for cellular activities like repairing muscle cells. The mitochondria in individuals with Duchenne are not very efficient at powering their cells. Therapies that target the mitochondria in muscle cells, which are able to make them work more efficiently, could improve activities like muscle repair.
The heart is a muscle that is affected by Duchenne. Maintaining heart function is very important, as it enables individuals with Duchenne to live longer. Some of the treatment approaches mentioned above can positively impact heart function, but there is still a lot of work to achieve this goal. Some medical manufactures are investigating drugs specifically focused on improving heart function.