Duchenne Treatment Options

Duchenne muscular dystrophy, abbreviated to DMD or Duchenne, is an inherited disease of progressive muscle weakness and muscle deterioration affecting about 1 in 3500 to 5000 boys. The absence of dystrophin in muscle causes repeated cycles of muscle damage and regeneration, which leads to life-threatening complications. There is no cure for DMD. Some therapeutic strategies help patients produce some functional dystrophin. Duchenne treatment options aim to lessen muscle damage, improve regeneration, or slow disease progression.

Treatment of Duchenne muscular dystrophy with supportive drug therapy

Corticosteroids

Normally inflammation has an important role in stimulating regeneration, but patients with DMD have prolonged inflammation which is thought to contribute to muscle damage. Corticosteroids are the mainstay treatment for DMD due to their anti-inflammatory action which aims to control symptoms and slow the progression of disease. Corticosteroids are a class of steroid hormones that include glucocorticoids, but sometimes the two terms are used interchangeably.

Prednisone and deflazacort are commonly used corticosteroids of the glucocorticoid type. Glucocorticoid therapy has been shown to protect muscle mass, muscle function, and lung function and decrease the progression of scoliosis. However, there are significant side effects with chronic daily glucocorticoid use including weight gain, cataracts, delayed puberty, hypertension, and diabetes. Other side effects include swelling in the face, acne, excessive hair growth, gastrointestinal symptoms, and behavioral changes.

Other approaches to target inflammation

Other treatment approaches that target inflammation are under investigation for DMD. These include cyclosporine, cytokine modulation with tumor necrosis factor-alpha (TNF-alpha), nitrous oxide regulation, and mitogens. These anti-inflammation treatments have not yet shown a benefit for DMD.

Targeted treatments for dystrophin mutations

Exon-skipping drugs

Exon-skipping drugs are designed to allow DMD patients to produce functional dystrophin protein by skipping over the mutated portion of the dystrophin gene. The DMD gene, dystrophin, is divided into 79 segments of genetic code called exons with exons 44 to 55 located in a region where mutations frequently occur.

The genetic code is like a series of three-letter words with no spaces that specify the sequence of protein building blocks to build that protein. To make the dystrophin protein, the DNA sequence is copied or transcribed into an RNA molecule which is then processed by joining the exons together. The translation machinery inside the cell reads the genetic code on the RNA transcript and builds the protein piece by piece, like adding beads to a string.

Frameshift mutations are when the number of letters inserted or deleted from the genetic code is not a multiple of three letters. This shifts the reading frame to specify completely different protein building blocks. In DMD this results in no functional dystrophin protein. Exon-skipping drugs for DMD target frameshift mutations. Exon-skipping drugs cause RNA transcripts to be processed so they skip the mutated exon and join the exons together in the correct reading frame. Because of the skipped portion, the resulting protein is shorter but still contains enough of the correct pieces to be a functional dystrophin protein.

Translational read-through inducing drugs

Nonsense mutations in the dystrophin gene change the genetic code to signal “stop, this is the end” which prevents the full protein from being produced. Translational read-through-inducing drugs fix this by causing the translation machinery to read through this premature stop signal and continue to build a functional protein.

Cellular therapy

Cellular therapies aim to boost the capacity for muscle regeneration. In muscle regeneration, muscle stem cells are activated to grow and form new muscle fibers. Repeating cycles of muscle damage and regeneration cause muscle stem cells to get used up quicker in DMD. The main goal of cellular therapy is to replenish the pool of muscle stem cells with precursor muscle cells or stem cells that can form muscle. Other DMD cellular therapies aim to use heart cells to improve both skeletal muscle and heart function. Different types of cellular therapies are under investigation in clinical trials for DMD.

myTomorrows offers a free service to help families find and access Duchenne Muscular Dystrophy clinical trials and other treatment options.