Developing a New Drug to Treat Duchenne Muscular Dystrophy

Justin Fallon

For 17 years, Justin Fallon has used microscopes and mice - classic tools of bench research - to study a protein called biglycan. The path started with a simple question: how does a muscle cell generate so much force, yet stay intact? Normal muscle has no problem with this task, but in a boy with Duchenne Muscular Dystrophy (DMD), the muscle cells can't withstand such stress and eventually die. DMD is the most common form of muscular dystrophy, striking about 1 in 3,500 boys. There are no effective treatments.

Fallon and his co-workers first discovered that a protein called biglycan organizes the system that protects muscle cells from damage and helps resist fatigue.  Importantly, the biglycan-based system is not affected by the genetic mutation that causes DMD.  Fallon and his team showed that muscles in dystrophic mice injected with recombinant biglycan show improved function and decreased damage. The implication for patients was clear: a biglycan treatment could slow the muscle damage caused by this incurable condition.

This discovery helped launch Tivorsan Pharmaceuticals, a Providence-based start-up company working toward human trials of biglycan. Fallon, a member of the Brown Institute for Brain Science and the Norman Prince Neurosciences Institute, is the founding scientist of Tivorsan.

Since its launch in 2010, Tivorsan has made major strides in developing biglycan as a potential therapy for DMD.  In 2011, Fallon won a major, $1.3 million award from the National Institutes of Health to accelerate preclinical development of biglycan. This year, Tivorsan received $1 million from the Muscular Dystrophy Association and $500,000 from Parent Project Muscular Dystrophy for its drug development work.

In February, the Fallon lab published new findings showing that biglycan is also a major player in stabilizing the connections between motor neurons and muscle. These results set the stage for testing biglycan as a potential treatment for diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis, or ALS.

"We are very enthusiastic about the prospects for biglycan as a potential therapy for DMD, and perhaps ALS," says Fallon.  "Our program is also a great example of how work in basic science can be translated to therapies that can help patients."