Individuals diagnosed with Duchenne muscular dystrophy (DMD) face few treatment options. DMD is a progressive muscle weakness and degeneration with loss of contractibility caused by one of several mutations in the DMD gene that leads to the chronic activation of a transcription factor called NF-κB—leading to the loss of the dystrophin protein in muscle cells.
DMD affects 3,500-6,000 male births and is the most common genetic neuromuscular disease. It is caused by one of several mutations in the DMD gene. No matter what the particular mutation, a key driver of muscle degeneration and suppression of muscle regeneration in DMD is chronic activation of the transcription factor NF-κB, which causes loss of dystrophin, a protein which helps keep muscle cells intact. Current therapeutics either assist only a subset of DMD patients who have a particular genetic mutation or cause significant side effects.
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However, a recent investigational drug called ‘edasalonexent’, an oral NF-κB inhibitor, may hold the potential to slow the progression of the disease. The drug was recently examined to hold no safety issues during a Phase I clinical trial. Paving the way for more clinical testing, results of the study were recently published in the Journal of Neuromuscular Diseases.
"In addition to being well tolerated in pediatric patients with DMD, our Phase 1 data demonstrated that edasalonexent (CAT-1004) inhibited NF-κB. This is important because NF-κB is a key link between the loss of dystrophin and disease progression in DMD. This would mean that edasalonexent has the potential to limit disease progression for all patients affected by DMD, regardless of their underlying mutation," explains Joanne Donovan, MD, PhD, Chief Medical Officer of Catabasis Pharmaceuticals, Inc. (Cambridge, MA, USA).
The drug, edasalonexent, is orally administered and that contains two active substances, salicylic acid and the omega-3 fatty acid docosahexaenoic acid (DHA). These two substances separately are inhibitors of NF-kB, but together they provide a more potent inhibition. "This shows that with short-term dosing, edasalonexent can directly reduce the levels of elevated NF-κB in circulating DMD mononuclear cells prior to any changes observable in muscles," notes Dr. Donovan.
Source: Science Daily
