Scientists used a safe virus to deliver a protein called follistatin into the leg muscles of young and older mice that have a disorder similar to human Duchenne muscular dystrophy (DMD). The protein inhibits the activity of myostatin, identified in previous research as a protein that limits muscle growth. Both young and old mice treated with the therapy responded with increased muscle mass and improvements in strength.
Patients with multiple different types of muscular dystrophy were divided into four groups given sequentially higher doses of a myostatin inhibitor called MYO-029 produced by Wyeth Pharmaceuticals. The new study, the first to evaluate a myostatin inhibitor in patients, assessed its safety in adults with muscular dystrophy and found that it was well-tolerated (safe).
Besides Wyeth Pharmaceuticals testing MYO-029 there are other companies working on myostatin inhibitors.
Amgen, the world’s largest biotechnology company, has started a safety trial for a myostatin blocker called AMG-745. McNickle declined to how say many patients are participating.
Acceleron, in Cambridge, Massachusetts, will begin safety trials this year for its myostatin treatment, ACE-031, said Steven Ertel, vice president of corporate development.
Agencies that police sports for performance-enhancing substances say myostatin blockers may reach athletes as soon as this year’s Olympics and certainly by 2012. Some athletes may already be using real myostatin inhibitors. There is a lot of fake myostatin inhibitors but athletes with access to good labs could have access now. Real myostatin inhibitors are being given to hundreds in disease trials now. A rogue lab could be built for as little as $500,000 to turn out untested materials to meet athletes’ demands.
Clearly elite athletes can afford to pay that price or have it provided by a national sports program.
Using a single injection, gene-delivery strategy involving FS, investigators treated the hind leg muscles of mice. Results showed increased muscle size and strength, quadruple that of mice treated with proteins other than FS. The muscle enhancements were shown to be well-tolerated for more than two years.
The mice used in this study as a model for DMD are called mdx mice. The older mdx mice received the therapy when they were 210 days old, at least a month after they showed significant hallmarks of their disease, including inflammation and fibrosis. When they were 560 days old, the treated mice showed robust muscles, with increased muscle fiber size along with reduced inflammation and less scarring compared to control-treated mdx mice.
In studies of younger mdx mice, the therapy was administered when they were 3 weeks old. At age 5 months, they had a larger body mass and higher muscle weight than did comparison animals.
Before testing follistatin in mdx mice, the scientists first tested the protein in normal mice and found after 725 days that they, too, had increased muscle mass and better grip strength when compared to untreated mice.
Previous research has shown that simply eliminating myostatin isn’t sufficient to improve muscle function in muscles of older DMD patients once progressive degeneration has begun. But the follistatin treatment in this latest study appeared to do more than just inhibit the effects of myostatin.
“This protein led to muscle enhancement, increased strength and lowered the effects of inflammation and fibrosis,” Kaspar said. “Because of those effects, we believe that it could be potentially useful for older Duchenne muscular dystrophy patients. And these results appear to translate to other muscle wasting diseases and aging, so it has potential to help a larger population of patients.”
After two years, the therapy in these studies showed no effects on reproductive function or cardiac function in the mice.
Insurance companies like Blue Cross are signing alliances with overseas hospitals (seven so far and hopes to add five more by yearend, including them all in coverage for his company’s 1.5 million members). Insurers could make this more enticing by waiving all deductibles and co-pays, offer to cover travel costs for the patient and family members, even throw in a cash incentive, and still save tens of thousands of dollars. After all, a heart procedure that costs $100,000 in the U.S. runs only $10,000 to $20,000 at some of the best private hospitals in Asia. And the quality of care? Foreign hospitals in such arrangements are typically approved by Joint Commission International, part of the same nonprofit organization that accredits American hospitals.
An assistant vice-president of health-care services at Blue Cross & Blue Shield of South Carolina, he has ample health benefits. But Boucher recently chose to have a colonoscopy at Bumrungrad International Hospital in Bangkok, mainly to make a point about the expanding options available to Blue Cross customers. And his company happily picked up the $640 tab—a bargain by U.S. standards.
Currently one of the gene therapy pioneers, Sweeney, has aided antidoping officials. “But I’ve often told WADA my position would change if [gene therapy] is proven to be safe,” he says. “Then we’re withholding something that would make the athletes healthier.”