More than a decade of targeted Muscular Dystrophy Association-funded research, made possible as a result of generous public support of the MDA Labor Day Telethon and thousands of grassroots special events, has culminated in MDA providing financial assistance for the start of the first phase 2 placebo-controlled, multiple-dose efficacy, safety, tolerability and pharmacokinetics clinical trial of an exon-51 skipping drug, eteplirsen, as a potential therapy for Duchenne muscular dystrophy (DMD).
The first three of 12 DMD boys participating in the AVI BioPharma clinical trial at Nationwide Children's Hospital in Columbus, Ohio, received the first of 24 weekly doses of eteplirsen or a placebo by intravenous infusion (i.v.). Four more participants had muscle biopsies vital to measuring the presence of the essential muscle protein dystrophin both before and after treatments. The seven boys traveling in for the study launch are from California, Illinois, Florida, Wisconsin, Virginia and Missouri.
"This is an important day for families fighting muscular dystrophy," said R. Rodney Howell, M.D., Chairman of the MDA Board of Directors. "AVI BioPharma already completed a 19-patient clinical trial in the United Kingdom confirming the potential of eteplirsen to be a safe and effective disease-modifying drug for DMD (The Lancet, July 25, 2011). Now, a team led by Dr. Jerry Mendell is receiving funding from MDA to help initiate this randomized, double-blind, placebo-controlled 12-patient trial needed to further test safety, efficacy and optimal dosing."
"Twenty-five years ago, MDA-funded investigators identified the dystrophin gene that, when mutated (or defective) causes Duchenne muscular dystrophy, as well as the somewhat milder Becker muscular dystrophy (BMD)," explained Mendell, Curran-Peters Chair of Pediatric Research at Nationwide Children's Hospital, and professor of pediatrics and neurology at Ohio State University. "Today, we're under way with a clinical trial of a drug that ultimately could create a shortened but functional dystrophin protein for DMD boys with certain out-of-frame gene deletions that may be corrected by skipping exon 51.
"By administering eteplirsen by i.v. for 24 weeks," Mendell added, "our goal is to find the best dosage to trick the body into skipping over genetic disruptions present in some cases of DMD, to produce dystrophin levels typical of Becker muscular dystrophy. In Becker many patients are able to walk into late adulthood and to have normal or near normal life spans."
The introduction of exon skipping to restore the open reading frame using splice-switching oligomers targeting dystrophin exons is one of several attractive therapeutic strategies for Duchenne muscular dystrophy being pioneered by MDA-funded investigators.
"MDA has been funding exon-skipping research for Duchenne muscular dystrophy for more than a decade," noted Valerie Cwik, M.D., MDA medical director and executive vice president for research. "We're very pleased to now be collaborating with AVI BioPharma on this trial and are hopeful that eteplirsen will become an effective therapy for those living with Duchenne muscular dystrophy."
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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.
In addition to funding more than 300 research projects worldwide, MDA maintains a national network of some 200 hospital-affiliated clinics; orchestrates hundreds of support groups for families affected by neuromuscular diseases; and facilitates extraordinary local summer camp opportunities for thousands of youngsters fighting progressive muscle diseases.
The Association is the first nonprofit to receive a Lifetime Achievement Award from the American Medical Association "for significant and lasting contributions to the health and welfare of humanity."
The Association's unparalleled programs are funded almost entirely by generous public contributions to the MDA Labor Day Telethon and by other grassroots fundraising events orchestrated by MDA year-round. The 2011 Telethon will be broadcast nationwide by some 150 television stations on Sunday, Sept. 4, from 6 p.m. to midnight in every time zone.
About AVI BioPharma
AVI BioPharma is focused on the discovery and development of novel RNA-based therapeutics for rare and infectious diseases, as well as other select disease targets. By leveraging a highly differentiated RNA-based technology platform, AVI has built a pipeline of potentially transformative therapeutic agents, including a clinical stage Duchenne muscular dystrophy candidate and anti-infective candidates for influenza and hemorrhagic fever viruses. AVI targets a broad range of diseases and disorders through distinct RNA-based mechanisms of action. Unlike siRNA and other RNA-based approaches, AVI technologies can be used to directly target both messenger RNA (mRNA) and precursor messenger RNA (pre-mRNA) to either downregulate (inhibit) or upregulate (promote) the expression of targeted genes or proteins.
About Nationwide Children's Hospital
As one of the largest and most comprehensive pediatric hospitals and research institutes in the United States, Nationwide Children's is a resource and an advocate for children and parents in central Ohio and far beyond. In fact, in a typical year, Nationwide Children's sees patients from across the country and around the world. The Research Institute at Nationwide Children's Hospital is one of the nation's 10 largest free-standing pediatric research centers and works to enhance the health of children by engaging in high-quality, cutting-edge research. The work carried out every day is dedicated to improving the health of children and their families in Central Ohio and beyond.