Justin Fallon, professor of medical science, has been conducting research on Duchenne muscular dystrophy for 25 years. Now, with the help of external partnerships, his discoveries could be employed in clinics.
Fallon's work deals with a drug called Biglycan, which has proven to be a potential therapy for DMD in humans.
"The most important thing is that we have identified our clinical candidate," he said, "meaning the actual compound or formulation of the drug."
Duchenne muscular dystrophy is a genetic, sex-linked disease primarily affecting males that gradually degrades the muscles of the body. The disease plays out over the course of decades. Victims are typically diagnosed by age five, though degeneration is slow to emerge. At 10 years, there is difficulty walking, and most motor ability is disabled by the late teens. Few live past their twenties.
Biglycan, Fallon said, is a recombinant protein that activates a chemical pathway which the body uses to develop muscles during early childhood.
This pathway is turned off in all individuals at a certain age, but those affected by the disease suffer from muscle degeneration as a result.
"What we're doing is working to reactivate that fetal pathway, which is good because the mechanism by which Biglycan works is a novel one," Fallon said.
Biglycan improves muscle function and encourages cell growth and regeneration, Fallon said. "There's no other drug for DMD that works in this particular way. We didn't know that going in, but we do know it now."
Though research is the most important phase, there are many other steps involved in taking a potential cure from concept to reality. One such step involves testing. So far, Biglycan has proved largely successful in lab animals, and recent evidence shows it is a good candidate for DMD therapy in humans.
"We've made a modified form of Biglycan that we intend to take into the clinic," Fallon said. "We will be doing a whole set of very formal safety studies to test that in a rigorous way."
Such studies help Fallon and his team eliminate potential dangers that could arise from the use of the drug. "So far we have not seen any signs of toxicity. We have not yet seen side effects, but it doesn't mean we won't see any," he said.
The team must also deal with dosage and manufacturing.
"We do have evidence that the level of dosing that we use is compatible for use in humans," he said. "Everything looks very promising. We can manufacture it, and it is well-tolerated."
Fallon stressed that "it will be possible to manufacture Biglycan with sufficiency and yield. We've done work showing the feasibility of manufacture."
The pharmaceutical company Tivorsan announced on Sept. 20 that it would be partnering with Fallon to license patents and conduct further research.
"Tivorsan's role is something that is very difficult to do in an academic setting," Fallon said. "Without that, we could not have moved toward the clinic."
Fallon's team has also worked with contract research organizations. "For manufacturing, it's been done externally. Efficacy measurements are done externally. We have network of outside labs that provide services." These groups do not necessarily drive the science, but are still important in running additional tests and other background work, Fallon said.
Fallon said his successes have come from years of work. "The finding that Biglycan regulates this pathway is the result of 25 years of work in my lab. And of those 25 years, 20 of that has been basic science. So all of this was made possible by a commitment to understanding how muscles work, and in this case how synapses work."
"Therapies don't come out of thin air," Fallon said. "To put a very simple analogy, a mechanic can fix your car because a good mechanic knows how your car works. When it comes to disease, we need to understand the body."
Scientists' knowledge of the body's function is still limited, Fallon said. "That is the value of research, and it is important to put that into context."
