Potential New Duchenne Muscular Dystrophy Treatment
Published : 2011-03-19
Author : Children's Hospital Boston
🛈 Synopsis : In DMD the combination of the lack of dystrophin and inflammatory reactions causes the muscles to weaken and waste over time.
Main DigestDrug Screen Points the Way to Potential New Duchenne Muscular Dystrophy Treatments - Zebrafish study highlights existing drugs that may help restore muscle in DMD.
Armed with a zebrafish model of Duchenne muscular dystrophy (DMD) and a library of 1,200 chemicals already approved for human use, researchers at Children's Hospital Boston have identified a compound that reverses the loss of muscle structure and function associated with DMD, seemingly by compensating for the loss of a critical protein. The discovery, published on March 14 in the online Early Edition of the Proceedings of the National Academy of Sciences (PNAS), opens up new avenues for understanding the physiology of DMD as well as a host of new potential therapeutic options.
The team was led by Genri Kawahara, PhD, and Louis Kunkel, PhD, director of the Program in Genomics at Children's. In 1987 Kunkel discovered the primary biological cause of DMD: the loss of the protein dystrophin, caused by mutations in its encoding gene.
DMD is one of 10 muscular dystrophies, a group of devastating, progressive, and incurable genetic diseases almost exclusively affecting boys. In DMD, the combination of the lack of dystrophin and inflammatory reactions causes the muscles to weaken and waste over time.
Using a zebrafish model of DMD, Kunkel and his collaborators set out to screen 1,200 chemicals already approved for human use for any that might have a restorative effect on muscle tissue. Of these 1,200, seven had the desired effect. One in particular, aminophylline, had a significantly stronger effect on the fishes' muscle structure and survival.
"The compound is not replacing the lost dystrophin protein in the fishes' muscles," said Children's Kunkel, who is also a professor of pediatrics and of genomics at Harvard Medical School, "but rather is compensating for that loss."
Aminophylline is an anti-inflammatory and is already in clinical use to treat asthma. A non-selective phosphodiesterase (PDE) inhibitor, it blocks the same biochemical pathway as sildenafil citrate (Viagra®, Pfizer). When studied in the zebrafish model, sildenafil also had a strong positive effect, similar to aminophylline. "We know that other groups have had positive results with sildenafil citrate salt in a mouse model of DMD," Kunkel noted. "The effects of PDE inhibitors in these models indicate that muscle vasculature may play a larger role in DMD than previously thought."
"The zebrafish have turned out to be an ideal vehicle for this kind of small molecule screening in DMD," Kunkel continued. "Because we can grow and test so many at a time, we were able to screen this chemical library very quickly, and the fact that our results reflect those of other groups using other models validates our screening strategy. We are already screening a few thousand more chemicals, and because we're focusing on ones that have already been approved for human use, we are confident that we will be able to take candidates found in the fish quickly through mouse studies and into the clinic."
The study was funded by National Institute of Neurological Disorders and Stroke and the Muscular Dystrophy Association.
Founded in 1869 as a 20-bed hospital for children, Children's Hospital Boston today is one of the nation's leading pediatric medical centers, the primary pediatric teaching hospital of Harvard Medical School, and the largest provider of health care to Massachusetts children. In addition to 392 pediatric and adolescent inpatient beds and more than 100 outpatient programs, Children's houses the world's largest research enterprise based at a pediatric medical center, where its discoveries benefit both children and adults. More than 1,100 scientists, including nine members of the National Academy of Sciences, 12 members of the Institute of Medicine and 13 members of the Howard Hughes Medical Institute comprise Children's research community.
Related Muscular Dystrophy Documents
- 1: Walker-Warburg Syndrome: Symptoms, Causes, Treatment : Walker-Warburg Syndrome is a rare genetic and multi-system disorder characterized by eye and brain abnormalities and muscle disease.
- 2: Becker's Muscular Dystrophy Information : Beckers Muscular Dystrophy is a form of inherited disorder characterized by progressive muscle weakness in the pelvis and legs.
- 3: Duchenne Muscular Dystrophy Facts and Information : Duchenne Muscular Dystrophy is a genetic degenerative diseases primarily affecting voluntary muscles and causing pain.
- 4: STAT3 Inhibitor Key to Making New Muscles : Cyclic bursts of a STAT3 inhibitor can replenish muscle stem cells and promote differentiation into muscle fibers. Findings are important step in developing and maintaining new muscle to treat muscle diseases.
- 5: FDA Approves First Drug to Treat Duchenne Muscular Dystrophy : U.S. Food and Drug Administration approves Exondys 51 (eteplirsen) injection to treat patients with Duchenne muscular dystrophy (DMD).
You're reading Disabled World. Be sure to check out our homepage for further informative disability news, reviews, exclusive stories and how-tos. You can also follow Disabled World on social media sites such as Twitter, Facebook, and LinkedIn.
Disclaimer: Disabled World provides general information only. Materials presented are in no way meant to be a substitute for professional medical care by a qualified practitioner, nor should they be construed as such. Any 3rd party offering or advertising on disabled-world.com does not constitute endorsement by Disabled World. View our Advertising Policy for further information. Please report outdated or inaccurate information to us.
Journal: Disabled World. Language: English (U.S.). Author: Children's Hospital Boston. Electronic Publication Date: 2011-03-19. Title: Potential New Duchenne Muscular Dystrophy Treatment, Source: <a href=https://www.disabled-world.com/disability/types/mobility/md/dmd-treatment.php>Potential New Duchenne Muscular Dystrophy Treatment</a>. Retrieved 2021-04-12, from https://www.disabled-world.com/disability/types/mobility/md/dmd-treatment.php - Reference: DW#266-7235.