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Faculty Spotlight: Jeffrey Guptill, MD, MHS

Tuesday, October 9, 2018

As Associate Director of the Duke Early Phase Clinical Research Unit (DEPRU), Jeffrey Guptill, MD, oversees dozens of clinical trials, both for the myasthenia gravis that is his passion and for traumatic brain injury, Parkinson’s disease, Duchenne muscular dystrophy, and other conditions. In this week’s Spotlight interview, Guptill talks to us about why he’s hopeful that academia and pharmacy will improve treatments for myasthenia gravis over the next several years. He also discusses the scope of DERPU’s work and how exercise, gardening, and diving keep him sane, centered, and engaged when he’s not at Duke.

What are your current responsibilities within the Neurology Department? What does your typical day look like?
I spend the equivalent of a day per week seeing patients or attending in the EMG lab. The majority of my time is spent on translational and clinical research. I have personal research interests in clinical and translational research in myasthenia gravis (MG). Currently, there are no means to predict response to the medications we use to treat patients. In addition, the oral medications we use cause widespread immune system suppression and can sometimes have serious side effects.

To overcome these unmet needs we are looking for biomarkers that will help clinicians select the appropriate treatments for patients, and we conducting mechanistic studies using immune cells from MG patients that will hopefully lead to more targeted therapies. The pharmaceutical industry’s role  in MG has increased substantially over the past five years and we are hopeful that we will have new, targeted treatment options in the near future.

In addition, with my prior training in clinical drug development I conduct a range of clinical trials for industry sponsors, the government, and investigators at Duke. This research takes place in the Duke Early Phase Clinical Research Unit (DEPRU) which is located in Duke South (Blue Zone). For these clinical trials my activities vary quite a bit. I write protocols, navigate sponsor relationships, perform study procedures, assess safety events, review study reports, and generally oversee the conduct of all aspects of the trials.

You’re also heavily involved with the Duke Clinical Research Institute (DCRI). What does that work involve, and how does it overlap with your work here at the Department?
My work at DCRI is primarily focused on the clinical trials performed at DEPRU (DEPRU is part of DCRI), though I also serve as coordinating PI for Dr. Don Sanders’ PROMISE-MG study. I am Associate Director of the DEPRU which has 55 employees specializing in various aspects of clinical trial conduct – clinical operations, nursing, study coordinators, regulatory specialists, lab staff, etc. Our studies are typically focused on clinical pharmacology (how does a drug move through the body) and safety endpoints, and they often enroll healthy volunteers.

To give you an idea of the scope of our work, last year we initiated 15 studies and provided clinical trial services in support of an additional 28 trials for Duke researchers. This amounted to approximately 2,300 study visits, and we enrolled 125 healthy volunteer study subjects in our studies. We enrolled 328 subjects last year alone for the Project Baseline study, which a collaborative study with Verily (Google), Stanford, and Duke.

At DEPRU we conduct quite a few neuroscience studies. We have active studies for therapeutics targeting Parkinson’s disease, Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, small fiber neuropathy, and traumatic brain injury. I am PI of a 10-year contract to provide phase 1 clinical trial services for the neuroscience branch of NIH, NINDS, and we should have a relatively steady stream of studies coming in the future. Many of the neuroscience studies we conduct require involvement from Department faculty, and I have been very fortunate to work closely on trials at DEPRU with many talented researchers in the Department, including Aatif Husain, Danny Laskowitz, Vern Juel, Shruti Raja, Lisa Gauger, Laurie Sanders, Jeff Cooney, Eddie Smith, and several others. I’ve learned a lot from them, and I’m always amazed at their generosity and dedication.

How and when did you first get interested in neurology? What drew you to study neuromuscular diseases in particular?
I took a psychobiology course in college and was blown away by the complexity of the nervous system, but also how cool it was! I became hooked on neuromuscular diseases during my residency rotation in the EMG lab. I had great mentors during that rotation and loved the procedural aspects of the EMG and how these studies were an extension of the clinical exam and could immediately test your hypothesis about what was going on with the patient.

How has our knowledge of and ability to treat neuromuscular disease changed the most since the start of your career? What’s the biggest advance that you see coming over the next decade?
The two biggest changes in my mind are understanding the genetics of neuromuscular diseases and, in my specific area, the understanding of how the immune system works, which has revolutionized how certain diseases are treated, particularly MS in neurology. I expect that new therapies for MG are on the horizon in the next three to five years. Also, it has taken a while but approaches for the effective delivery of gene-based therapies are advancing and I hope that will translate to major advances in the next decade. We are seeing the leading edge of this revolution (I’m hopeful) with the first approved treatment for spinal muscular atrophy last year.

What other passions or hobbies do you have outside of the Department?

I guess I’d say I have three hobbies – exercise, gardening, and diving. Exercise keeps me sane, and if I don’t, I think it greatly affects my mood and productivity. I like being outdoors, so gardening has become somewhat of a hobby for me – good crop of cucumbers and peppers this year. Finally, I love scuba diving and have an advanced open water certification. Unfortunately, I don’t get to do that as much as I’d like. I’m not sure Wayne Massey approves of this hobby, given his expertise in dive medicine, though he hasn’t told me directly. Diving is like being on another planet – feeling weightless, getting to see amazing creatures, and I like the technical aspects of it. And it’s very peaceful (no cellphones).

Guptill and daughter
Guptill basks in glory after completing a "mud run" race with his daughter.