MDA AWARDS HARVARD RESEARCHER $375K TO SCREEN 4,000 DRUGS AS POSSIBLE TREATMENTS FOR DUCHENNE MUSCULAR DYSTROPHY

TUCSON, Ariz., Aug. 18, 2010 — Call it extensive. Call it exhaustive. Call it important. Louis M. Kunkel, Ph.D., the scientist who, 24 years ago, led the successful hunt for the flawed gene responsible for Duchenne muscular dystrophy (DMD), is today turning to the common aquarium zebrafish in his quest for drug treatments for the devastating muscle disease.

Kunkel, is using the fish, harboring a mutation in the very gene he discovered in 1986, as “biological test tubes” to rapidly test some 4,000 drugs that are currently approved for human use for other medical conditions, to determine which may hold the greatest promise as a treatment for Duchenne muscular dystrophy and its less severe counterpart, Becker muscular dystrophy (BMD).  Both of these progressive muscle-degenerating diseases result from mutations in the dystrophin gene.

The innovative screen will be financed with a $375,000 research grant from the Muscular Dystrophy Association, which also funded the landmark 1986 hunt for the dystrophin gene. 
Zebrafish are the perfect initial screening choice, Kunkel explains, because they can be cultured in large numbers, develop rapidly, are permeable to small molecules, and are transparent early in life. 

Louis M. Kunkel, Ph.D.

“We can place the compounds in the fish water and the zebrafish swim around and absorb the compound. It’s a novel way of going at this, to use a small organism to look for things to improve the outcome of dystrophin deficiency. And, you can actually see the muscle tearing apart when the zebrafish swim. Dystrophin deficiency is probably more severe to zebrafish than it is to the mdx mouse (an experimental mouse model for Duchenne dystrophy). Mostly, it’s because zebrafish need muscle right away to swim."

Using these time- and cost-efficient screens already has enabled Kunkel’s team at Children’s Hospital Boston to identify seven compounds that increase the survival rate of these dystrophin deficient fish from 10 percent to as much as 60 percent.

The new three-year project has three primary objectives: to identify additional compounds that stop or slow disease progression in dystrophin deficient zebrafish; to determine the mechanism and measure the long-term effects of each drug; and to further test any compound found to alter disease progression in zebrafish in available dystrophic mouse models.

“You name it and we are testing it,’’ said Kunkel, professor of pediatrics and genetics at Children’s Hospital Boston. “If it’s used in humans, it is part of this library. It’s about 4,000 drugs. We’re looking at which ones work the best, and we’re looking at families of compounds to see if there are additional things out there that might work better.’’

Kunkel is one of 38 research leaders receiving new multiyear research grants from MDA. His project is part of the $14.1 million in new research funding approved during the Association’s July Board meeting. Originally attracted to the field of neuromuscular disease research by an MDA Developmental Grant, this is Kunkel’s 14th MDA grant, bringing the Association’s total investment in his pioneering efforts to more than $2.3 million.

According to R. Rodney Howell, M.D., chairman of the MDA Board of Directors, “Generous Americans responding to the annual Jerry Lewis MDA Telethon, and to thousands of other special events benefiting the families served by MDA, deserve much of the credit for the rapid progress being made toward treatments for neuromuscular diseases. It’s their strong belief in MDA’s capable stewardship of public funds that’s enabling so much to be accomplished — even in a sluggish economy.’’

Research grant applications are peer-reviewed twice yearly by MDA’s Medical and Scientific Advisory Committees, comprising world-renowned experts in neuromuscular disease research.  The most promising of some 500 applications received each year are recommended for funding to the MDA Board of Directors. Grant applications submitted by Committee members, including Kunkel, who chairs MDA’s Scientific Advisory Committee, are reviewed separately by an independent panel of scientific and medical experts.

“You will not find a more persistent or innovative scientist than Lou Kunkel,” said Howell, adding that “ever since the watershed moment when he identified the genetic cause for Duchenne and Becker muscular dystrophies, Kunkel has been a true champion for gene and cell therapy pathways to treat these progressive diseases. Now, he’s leading the charge for alternative small molecule therapies that could complement existing therapeutic approaches.” 

Often credited for its leadership in building the field of neuromuscular disease research, MDA has also enhanced clinical care for individuals affected by muscle disorders, achieving important quality of life and longevity gains. The Association, which has invested almost $39 million in 2010 in research worldwide, is the first nonprofit to earn a Lifetime Achievement Award from the American Medical Association (“for significant and lasting contributions to the health and welfare of humanity”).

MDA-funded scientists have uncovered the genetic defects that cause several forms of muscular dystrophy; Charcot-Marie-Tooth disease (CMT); a form of amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease); childhood spinal muscular atrophy (SMA) and other neuromuscular conditions. Now entering a period of increasing numbers of clinical trials of potential therapeutics, the Association’s network of approximately 200 hospital-affiliated clinics is instrumental in identifying appropriate candidates for clinical trials; and to help refine outcome measures for those clinical trials.

More than 1 million people in America are affected by neuromuscular diseases. 

In the Boston area, individuals affected by any of the more than 40 muscle diseases in MDA's program can receive excellent medical care at the MDA Clinics at Brigham & Women’s Hospital, Children’s Hospital Boston, Massachusetts General Hospital and TUFTS Medical Center Hospital.

MDA is the nonprofit health agency dedicated to curing muscular dystrophy, ALS and related diseases by funding worldwide research. The Association also provides comprehensive health care and support services, advocacy and education. For more information on MDA research and programs, go to www.mda.org. 

For more information about these new grants, visit MDA's "Grants at a Glance," an online slideshow that showcases each grant with photos and detailed information.