Prof.’s muscular dystrophy drug shows promise

By
Wednesday, January 23, 2008

Justin Fallon, professor of medical science, began researching Duchenne muscular dystrophy in 1985 and currently heads a lab developing a treatment for the disorder. But with the help of a Brown alum’s business and medical expertise, that treatment could be in pharmacies within five to seven years.

Along with his lab, Fallon has developed a drug called Biglycan, which stimulates the cells affected by DMD, forcing them to continue producing an important protein people normally lose around the age of four or five.

While Biglycan has proven successful in diminishing muscle degeneration in lab mice, making it available for human use requires “a complicated, expensive process with many demands,” Fallon said.

The drug needs to undergo rounds of testing to ensure its safety before it receives approval from the Food and Drug Administration. Biglycan must be produced in “highly controlled conditions” outside of his lab space to ensure its safety, Fallon said. By the end of last spring, Fallon had reached a roadblock, putting further development of Biglycan “beyond the expertise and capabilities of (his) lab.”

When Fallon was asked in June to give physician John Nicholson ’72 a tour of the new Sidney Frank Hall for Life Sciences, he explained his research and Nicholson agreed to return to Brown to look further into the project.

“I appreciated his passion for it more than anything else, his intellect and his passion,” Nicholson said. The two formed Tivorsan Pharmaceuticals, a company dedicated to further development of the Biglycan treatment.

“The whole purpose of the company was to surround this incredible protein scientist with a network of necessary scientists and regulatory people and organizational people… to get this one-man band playing in an orchestra,” Nicholson said.

“John has an extensive network of people who are on the development and business side, which is what we needed,” Fallon said.

Help from “finance types and other operational people” has garnered more support for Tivorsan’s work on Biglycan by bringing in business development expertise, drawing investors and forming a successful company, he added.

“Together we’ve built a team, and we’ve gotten support from patient advocacy groups, which are very committed to getting this therapy done,” Fallon said.

Two particular patient advocacy groups, Parent Project MD and Charley’s Fund, are enthusiastic about Fallon’s research because of their own close connections to the disease. In addition, the lab continually applies for government grants to supplement advocacy aid.

DMD is the most common form of muscular dystrophy, representing 80 to 90 percent of cases. The disease affects only boys, slowly destroying their muscles until their late teens or early twenties, when they become paralyzed and require respiratory assistance, Fallon said.

“Over the course of this disease, picked up when you’re four or five, you can write the script about what’s going to happen to these kids for the next twenty years of their life,” Fallon said. “It’s remarkably predictable.”

The disease is caused by the absence of dystrophin, a protein that enables muscle movement. This makes muscle cells unable to perform common functions such as walking and, later on, breathing. Symptoms first appear when boys are four or five years old, not at birth or in prenatal stages, because the protein utrophin does dystrophin’s work in early childhood, Fallon said.

Fallon’s lab, which employs undergraduate and graduate students and post-doctoral fellows, researches the details of the disease and possible treatments.

“It’s going very well,” Fallon said of the search for a DMD treatment.

Biglycan works by stimulating muscle cells to produce utrophin, which can give DMD patients muscle function.

While Fallon researches Biglycan, other labs are researching alternate treatments, he said. Because DMD is a rare disease, affecting 1 in 3,000 boys, funding is limited. Both Fallon and Nicholson stress how early in the development process Biglycan currently is. “This still remains a one-mouse model opportunity,” Nicholson said. “The translation of this to the human is still very, very risky.”

Fallon told The Herald he hopes to have Biglycan tested clinically, on real patients as opposed to mice, within two years. If it is safe, he hopes it can be through clinical trials and available to DMD patients within five to seven years.

“We are working extremely hard to make that happen,” Fallon said. “As fast as we can move, consistent with safety, we will.”