Emerging drugs for Duchenne muscular dystrophy.
BACKGROUND
Duchenne muscular dystrophy (DMD) is the most common, severe childhood form of muscular dystrophy. Treatment is limited to glucocorticoids that have the benefit of prolonging ambulation by approximately 2 years and preventing scoliosis. Finding a more satisfactory treatment should focus on maintaining long-term efficacy with a minimal side effect profile.


METHODS
Authors discuss different therapeutic strategies that have been used in pre-clinical and clinical settings.


CONCLUSIONS
Multiple treatment approaches have emerged. Most attractive are molecular-based therapies that can express the missing dystrophin protein (exon skipping or mutation suppression) or a surrogate gene product (utrophin). Other approaches include increasing the strength of muscles (myostatin inhibitors), reducing muscle fibrosis and decreasing oxidative stress. Additional targets include inhibiting NF-κB to reduce inflammation or promoting skeletal muscle blood flow and muscle contractility using phosphodiesterase inhibitors or nitric oxide (NO) donors. The potential for each of these treatment strategies to enter clinical trials is a central theme of discussion. The review emphasizes that the goal of treatment should be to find a product at least as good as glucocorticoids with a lower side effect profile or with a significant glucocorticoid sparing effect.
The Ohio State University, Research Institute, Nationwide Children's Hospital and, Department of Pediatrics, Columbus, OH 43205, USA.
Vinod
V
Malik
Louise R
LR
Rodino-Klapac
Jerry R
JR
Mendell
D000818:Animals; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D005938:Glucocorticoids / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic
D005938:Glucocorticoids