A novel treatment in development at the University of Nevada School of Medicine for the most common form of muscular dystrophy is advancing towards human trials with a $308,000 boost from the Muscular Dystrophy Association.
The grant will be used to expand successful research by Associate Professor of Pharmacology Dean Burkin that has shown his laminin-111 protein therapy prevents the onset of the devastating neuromuscular disease in mouse models.
"The early results for laminin-111 as a therapeutic agent for (Duchenne muscular dystrophy) are really exciting," Sanjay Bidichandani, MDA vice president of research, said. "We are eager to see this research go forward."
Duchenne muscular dystrophy is a lethal genetic disease that affects one in 3,500 newborn boys and is caused by mutations in the gene encoding dystrophin. There is no effective treatment or cure.
At the time of diagnosis, DMD patients usually have developed significant muscle disease. The three-year grant will help determine if Burkin's therapy is effective at preventing or reversing disease progression after onset.
"What we aim to discover now is if this therapy is effective at preventing or reversing disease progression after it has already started," he said. "First we will determine if laminin-111 prevents muscle damage after disease onset, preserves muscle function and improves survival of mouse models of DMD. Second, we will determine if laminin-111 prevents cardiomyopathy in mouse models of DMD.
"Finally, in collaboration with researchers at Texas A&M, we will determine if a human version of the protein prevents muscle disease in other animals afflicted with the disease. Results from these studies will pave the way towards developing human recombinant laminin-111 protein as a novel therapeutic for DMD."
Demonstrating that the human version has efficacy in animals with DMD will move this therapy closer to a Food and Drug Administration investigational drug application and potential human clinical trials.
"This MDA grant is a tremendous help in moving this technology forward," Burkin said. "Patients have been waiting a long time for therapies to come about and I think we're at the cusp of major discoveries. Theoretically, laminin-111 protein therapy should be able to treat all patients with Duchenne muscular dystrophy."
Since laminin-111 is a naturally occurring protein already present in our kidneys and other tissues, Burkin said there is a better likelihood that it would not be rejected by the human body.
A postdoctoral researcher in Burkin's lab, Ryan Wuebbles, also received an $180,000 MDA development grant over three years to investigate if laminin fragments can be therapeutic for the treatment of DMD. Wuebbles plans to test different parts of laminin-111 in cells cultured from animals and people with the disease. The most promising of these will be tested and compared to those generated by the full-length protein.
Burkin's work has been funded by the National Institutes of Health and he has a patent license agreement with a biotech company to develop the laminin technology.
His research has been profiled in the internationally acclaimed Better World Report, the American Journal of Pathology and the Proceedings of the National Academy of Sciences. He co-hosted the Myomatrix 2012 conference in April, which brought together 73 international scientists and clinicians to the University of Nevada, Reno campus to explore and share their latest findings and data on treatment breakthroughs related to congenital muscular dystrophy. The results of the Myomatrix Conference were published in the July issue of Neuromuscular Disorders.
In an article published in June in Science Translational Medicine Burkin summarized the impact of a new protein therapeutic, MG53, for the treatment of Duchenne muscular dystrophy.
Burkin, a New Zealand native, received undergraduate degrees in biology and developmental biology from Victoria University of Wellington, New Zealand. He completed his doctorate in biochemistry and genetics at the University of Colorado Health Sciences Center and postdoctoral training at Cambridge University, England. He then joined the University of Illinois to complete postdoctoral research before coming to the School of Medicine in 2003.