Duchenne Muscular Dystrophy: Research Takes Personal Turn for UCLA Scientists

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Stanley Nelson, MD, is a professor in the Department of Human Genetics at the University of California, Los Angeles (UCLA); his wife, Carrie Miceli, PhD, is a professor at the UCLA Department of Microbiology, Immunology, and Molecular Genetics. Both are researchers in the quest to find better therapies and even a possible cure for Duchenne muscular dystrophy (DMD), the most frequent and most lethal form of muscular dystrophy (MD). They are also parents to two boys, Calvin, 18, who entered college this year, and Dylan, 11, who was born with DMD.

While Dylan entered the world carrying a heavy genetic burden, he has two powerful forces going for him: his loving, caring parents who have the knowledge and skills to fight to find better therapies and solutions.

In 2008, the husband-and-wife team made a huge stride in their professional and personal efforts in the search for new treatments for DMD. With funding assistance from several private and government organizations, they opened the Center for Duchenne Muscular Dystrophy at UCLA (CDMD@UCLA) to support clinical care and translational research. Along with Melissa Spencer, PhD, a professor of neurology at UCLA, they serve as the center's directors.

CDMD@UCLA investigators are involved in several new research areas, among them, exon-skipping therapy. In DMD, lack of the protein dystrophin causes muscle deterioration and breakdown, leading to the devastating effects of the disease. Exon skipping has been likened to a "band-aid" to skip over the parts of the gene that block the effective creation of this essential protein.

Among other projects, center investigators are searching for drugs to enhance the effectiveness of exon skipping, using such techniques as high throughput screening (HTS) and repurposing drugs already approved by the Food and Drug Administration (FDA) for other conditions, but which also show promise for DMD therapy. HTS technologies enable researchers to rapidly identify active compounds, antibodies, or genes that modulate a particular biomolecular pathway, thus providing starting points for drug design, among other uses. Exon-skipping drug therapies are currently in human clinical trials, Nelson says.

Dylan's Role

Dylan, too, has played a part in various clinical trials. "He feels good about helping other boys with Duchenne muscular dystrophy," Miceli says. He has participated in a natural history study tracing progression of the disease and is currently participating in a drug-therapy study in cooperation with Cedars-Sinai Medical Center, Los Angeles, to determine if Viagra® and related drugs can improve muscle blood flow in DMD patients. Improved blood flow is predicted to lessen the damage to contracting skeletal muscles, thus reducing and slowing muscle damage and deterioration.

"Dylan is also traveling to Florida to participate in an imaging study," Nelson says. "This study examines whether or not using imaging instead of function tests will give us a more accurate picture of how the disease is progressing and what effect therapies are having. Dylan also gets to go to Disney World, which he's excited about."

At age 11, Dylan's muscles are weakening more. He no longer can participate in sports, has difficulty with stairs, and uses a scooter for some activities, such as field trips. Current medical care includes corticosteroids, angiotensin-converting-enzyme (ACE) inhibitors to slow development of cardiomyopathy, and nutritional supplements. Dylan uses night-time orthoses to keep his Achilles tendon stretched to avoid contractures and alleviate toe walking, and has a daily stretching routine.

Miceli strongly urges parents to enlist the help of a multidisciplinary team. "The literature is quite clear that multidisciplinary care can add 1015 years to life expectancy." She also urges parents not to accept the fatalistic view of some physicians that their son likely will only live into his teens or early 20s. "With good care and a multidisplinary team, life expectancy is being pushed up into the 20s and 30s [with some patients living into their 40s]. And promising clinical trials are coming down the pike."

As for Dylan, in spite of the debilitating effects of DMD, "He is a happy, cheerful boy," Miceli says. Dylan—and his parents—are glad that all their efforts may not only help him, but also all the other boys with DMD.



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