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Prospective molecular and genetic strategy is close to conquering muscular dystrophy

  • 6/25/2014 7:36:00 AM
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Yang Lee, M.S.

Duchenne muscular dystrophy (DMD) is the most prevalent and severe type of muscular dystrophy, affecting 1 in every 3500 newborn boys, according to the National Human Genome Research Institute. DMD causes progressive muscle weakness, cardiomyopathy, and respiratory failure. Patients are diagnosed when they are toddlers, become wheelchair-dependent in their early teens, and die usually before in their 30s. It has been more than 20 years since scientists identified the protein encoded by the defective gene that causes DMD; however, effective treatment methods to attenuate the DMD patient’s progressive muscle degeneration are still obscure. Many therapeutic prospects have been developed including non-invasive ventilation, steroid, and cardioprotective treatment that might enable to attenuate muscle weakness, but these treatments also have reported different side effects and sometimes toxicity. Most importantly, these treatments might be able to slow down or weaken the disease, but cannot prevent or stop it. In addition, stem cell therapy, boosting gene expression, and reintroducing old drugs have been examined as prospective therapies, but their clinical effects have not yet been determined.

Recently, a new molecular genetic strategy has received a high score as a potential DMD therapy because it causes severe DMD to convert to mild form Becker muscular dystrophy (BMD). This tool is called exon skipping and has been demonstrated to provide a successful outcome. Briefly, induction exon skipping restores the open reading frame by splice-switching oligomers, indicating dystrophin restoring in DMD patients. Studies have shown significant new dystrophin protein expression with no serious adverse events. Also, other dystrophin-related proteins were resynthesized and restored at the sarcolemma (muscle cell membrane) with lowered inflammatory indication. Judith C van Deutekom from Leiden University Medical Center, Netherlands also showed that specifically skipping exon 51 allows restoring open reading from the transcript region,resulting in mild dystrophin synthesis in DMD patients aged 8-16 years.

Treatment of DMD using the exon skipping technique looks very positive, yet needs more time to observe long-term whether restored dystrophin truly improved the quality of life for DMD patients by enabling them to have a normal life and/or extending their lifespan.


Further Reading:

  1. Sebahattin Cirak et al. Exon Skipping and Dystrophin Restoration in Patients with Duchenne Muscular Dystrophy after Systemic Phosphorodiamidate Morpholino Oligomer Treatment: an Open-Label, Phase 2, Dose-Escalation Study. The Lancet 378 (13) 595-605, 2011.
  2. Sebahattin Cirak et al. Restoration of the Dystrophin-Associated-Glycoprotein Complex After Exon Skipping Therapyin Duchenne Muscular Dystrophy. The American Society of Gene & Cell Therapy 20 (2) 462-467, 2012.
  3. Joel R Chamberlain & Jeffery S Chamberlain. Gene Therapies for Muscular Dystrophy Target RNA. Nature Medicine 16 (2) 170-171, 2010.
  4. Judith C van Deutekom et al. Local Dystrophin Restoration with Antisense Oligonucleotide PRO051, The New England Journal of Medicine 357(26) 2677-2686, 2007.



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