Dantrolene shows promise for treating DMD
medwireNews: A muscle relaxant called dantrolene used for treating malignant hyperthermia boosts the activity of therapies currently being developed to treat the genetic disorder Duchenne muscular dystrophy (DMD), show study findings.
DMD causes muscle weakness and loss, and eventual death triggered by frameshifting deletions in the DMD gene that lead to a lack of the protein dystrophin.
Current therapies in development trigger antisense oligonucleotide-mediated exon skipping, which restores the reading frame of the DMD gene and allows production of dystrophin. However, to date, only small amounts of dystrophin have been produced using this method.
As reported in Science Translational Medicine, Stanley Nelson (University of California, Los Angeles, USA) and team found that dantrolene promotes the activity of drugs that stimulate antisense oligonucleotide-mediated exon skipping allowing a much greater amount of dystrophin to be produced.
"Dantrolene is such an attractive candidate to test in this disease as it's already approved, has been used safely in humans for decades and we won't have to go through the lengthy and costly drug development process," Nelson commented in a press statement.
"We were very pleased to find out that this drug seems to work synergistically with the drugs being tested now on boys with DMD."
The authors identified dantrolene as a potential candidate for enhancing oligonucleotide-mediated exon skipping through a small-molecule screen of existing drugs.
When tested in a mouse model of DMD, the animals showed significantly improved muscle function and produced greater amounts of dystrophin when treated with a combination of the exon-skipping drugs and dantrolene as opposed to the exon-skipping drugs alone.
The researchers plan to carry out longer-term studies in mice to confirm their findings and then to proceed to clinical trials.
"These findings highlight the value of combination therapies and the repurposing of [US Food and Drug Administration]-approved medications as powerful translational strategies," conclude the authors.
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By Helen Albert, Senior medwireNews Reporter