On Tuesday May 20th, Dr. Justin Fallon visited the Circle to discuss his works that revolve around the question of “how to fix a problem when something goes wrong.” As a professor of neuroscience at Brown University, Dr. Fallon has contributed to the treatment of a disease called Duchenne’s muscular dystrophy (DMD) through his extensive research on the synapse between motor neurons and the muscle, and his co-founding of Tivorsan Pharmaceuticals.
DMD is a genetic disease that causes muscle degeneration in patients even after a small amount of muscle activity. Patients diagnosed with DMD have a mutation in their genes that codes for a protein called dystrophin, which is crucial to the regeneration of muscle. As a result, the muscles of patients with DMD get progressively weaker as they are used.
As the symptoms of DMD grow worse, patients lose their ability to use certain muscles. The muscle deterioration first affects the larger muscles in the body and slowly spreads to the smaller ones. With time, DMD can limit the muscle functions of the heart and diaphragm.
Because of its degeneration of vital organs, DMD can be a fatal disease; very few patients live beyond their 20s. Although some patients are still able to engage in daily routines thanks to the help of modern technology, the burden on both them and their caregivers is enormous. As a result, Dr. Fallon’s contributions to addressing this disease are viewed with great interest in the world of therapeutics.
Simply put, Dr. Fallon’s suggestion was to replace the lost dystrophin with a different protein called utrophin. Both dystrophin and utrophin function similarly to protect the muscle from damage. Dystrophin is created as one’s cells mature and the utrophin disappears.
As successful as Dr. Fallon was, he admitted that he did not know if there would be a day when he would reap all of these satisfying results when he first delved into the field of research.
Dr. Fallon says he was an enthusiastic biology student ever since middle school. Throughout the years, he met many great teachers who helped him solidify his passion for biology, but he says that he had little experience working in a lab even as an undergraduate student majoring in biology. At that point, he was still unsure of what field of sciences he wanted to focus on.
It was the summer after his first year of graduate school when things started to take off for Dr. Fallon. After joining a ten-week intensive course at the Marine Biology Laboratory in Cape Cod, he realized his interest in cell biology.
Afterwards, he spent three and a half years at the University College London as an NIH Postdoctoral Fellow where he worked with glial cells. Then, at Stanford University, he began to look at the synapse between motor neurons and the muscle. At Stanford he also learned about agrin, a protein that works in the extracellular matrix (outside the cell) that has high information content about muscular development.
The discovery of agrin ushered in a series of new findings for Dr. Fallon. Once he understood that agrin is critical in intra-cellular communication, he delved deeper into the mechanisms by which agrin works. Three years of research led him to find that dystroglycan is the key agrin-receptor in question. After four years of further research, he discovered that dystroglycan also binds to biglycan, the core protein in Dr. Fallon’s proposed therapy for DMD. The pieces of the puzzle were falling into place.
Looking back at Dr. Fallon’s journey, it seems as if everything worked out in an orderly fashion. However, this was not the case for Dr. Fallon when he first decided to pioneer across this unknown field of science. He said that “the hardest thing about research is that research by its nature is very uncertain. You spend the majority of your time getting things wrong and wondering how to do it right. Hopefully, that process will teach you and guide you for later research.”
It is also interesting to note that the first lab that Dr. Fallon worked in as a graduate student was in a unit founded by Darwin Prockop, a leading biochemist in the extracellular matrix and the father of Groton’s very own Mr. Dave Prockop. Back then, Dr. Fallon did not know that his later work would be so related to the extracellular matrix, but he says that his time at Dr. Prockop’s lab had really served him well.
During this process that requires much patience, Dr. Fallon said that knowing that his research has the potential to become a therapy to cure millions affected with DMD was a huge motivation. This knowledge led him to co-found Tivorsan Pharmaceuticals, a company that distributes what Dr. Fallon has discovered in his labs to be used as cures for DMD. Starting as an uncertain biology student, Dr. Fallon has accomplished something that was previously thought to have been impossible. In the words of Dr. Fallon, “You never know until you get there.”