Eric Hoffman speaks to the Binghamton University Forum

Eric Hoffman, professor and associate dean for research at Binghamton University’s School of Pharmacy and Pharmaceutical Sciences, spoke on the topic of “Interdisciplinary Research Centers Tackling Thorny Problems: Muscular Dystrophy, Opioids and Lyme” at the Binghamton University Forum luncheon April 30.

A geneticist, Hoffman focuses his research on the genetic basis of human and animal disease, drug development and genetic variation in human populations. He also facilitates drug development by bridging academic research, stakeholder foundations, governments and for-profits, including through establishment of interdisciplinary research centers.

Hoffman has been on a quest to find therapies to treat Duchenne muscular dystrophy since, as a postdoctoral fellow, he discovered the defect protein ─ dystrophin ─ that causes the most common and most severe fatal form of muscular dystrophy known as Duchenne (DMD).

“It’s the most common inherited disease and the most common treatment is daily high doses of glucocorticoids,” Hoffman told the audience. “These glucocorticoids are the standard of care, but the side effects they cause are just terrible.”

To facilitate research into DMD, Hoffmann has also been building collaborative research centers for more than 25 years.

“What are centers?” he asked. “The word is only as good as its definition, but here I’m talking about multidisciplinary and multi-institutional, broad, collaborative approaches to difficult research problems that are transnational, include the active involvement of stakeholders and have broad-based financial support.”

The centers Hoffman and colleagues have developed are international collaborations to try to figure out what causes the muscles of those with DMD to leak into the bloodstream and disappear over 10 to 15 years, with death of respiratory failure by the early 20s.

“Why is the disease so progressive?” he asked. “If we learned early on that dystrophin was missing when child was a fetus, why didn’t that child show symptoms until first grade? Dystrophin didn’t change over that time, but the disease did. I’ve spent much of my career looking at this.”

The problem, Hoffman said, is that no delivery system can handle the process of replacing dystrophin. Muscle is the largest organ system in the body and it’s just too big. And the dystrophin deficiency alone may not equal disability, but downstream events in specific muscles and at specific ages devolve into muscle loss and weakness.

“And because DMD is a progressive disease, if we try therapies too late, there is no muscle left to rescue,” he added.

To advance DMD research and through the centralized infrastructure of a center, a consortium (CINRG) was formed with 25 clinicians in 12 countries, all recruiting patients and participating in studies of DMD, Hoffman said. “We created a patient frozen muscle bank and everything is shared. No faculty own anything.”

Then in 2001, the Muscular Dystrophy Care Act was passed that created the first National Institutes of Health (NIH) Muscular Dystrophy Centers nationally, and resulted in the first Centers for Disease Control and Prevention funding and a first coordination of NIH research into DMD.

What followed was major support from the Department of Defense for the CINRG consortium clinical trial network, mouse drug testing facilities and the first research into why glucocorticoids work in DMD.

And where are we today? Hoffman said that through the center model developed and demonstrated by the CINRG consortium, international collaborations and working groups and working together with non-profits and governments in ways that make a difference.

From 1998 to 2000, no clinical studies had been done for DMD, Hoffman said, but in 2019, there are 250 studies in the database for DMD, with about 60 of them actively recruiting patients. “We’re building enthusiasm and working collaboratively,” he said.

The synergy created through our collaborative center has resulted in two therapies, Hoffman said: one to put dystrophin back and the other to activate danger signals.

He and colleagues Kanneboyina Nagaraju, professor and founding chair of the Department of Pharmaceutical Sciences at Binghamton, and chemist John McCall established ReveraGen BioPharma, a company that focuses on drug development. “We ‘tweaked steroids a bit’ to create vamorolone, a drug that has changed how steroids function to rid them of their side effects.”

Vamorolone is in Phase 3 clinical trials being run in eight countries and is “not only slowing down the disease, but making patients better,” Hoffman said. “There’s no growth stunting and as far as we can tell, no side effects at all. It’s looking like we’re heading toward approval next year.”

Hoffman said that, in addition to the DMD center, two others on campus are following the collaborative model: The Opioid Research Center of Central New York that is directed by William Eggleston, clinical assistant professor of pharmacy practice at Binghamton, and the Lyme Disease Research Center directed by Binghamton Professor of Anthropology Ralph Garruto.

The ORCC-NY has just sent in a grant proposal to study if online-based naloxone training can be used to lessen the number of people who are dying from opioid use disorder (OUD) in rural areas, where the death rate is higher than in urban areas. Another grant proposal would help fund a study in conjunction with UHS hospitals that would address the problem of babies being born to opioid-addicted mothers. The ORCC-NY is also initiating a program to enroll patients with OUD in treatment programs when they are being treated in an emergency room.

The Lyme Disease Research Center is working to improve current diagnostic tools and working with public health departments to assist in risk assessment and extend and enhance surveillance.