“It is exciting to think that what started as research in cells ... could one day have an impact on patients.”
Oren Levy, M.D., Ph.D.
When scientists and doctors can work together in the fight against Parkinson’s disease (PD) — comparing insights from the lab and clinic — isn’t the pace of science bound to accelerate? That has always been the philosophy of the Parkinson’s Disease Foundation (PDF).
The idea works even better when the scientist and the doctor are the same person. One of these is Oren Levy, M.D., Ph.D., Assistant Professor of Neurology at the PDF Research Center at Columbia University Medical Center. Dr. Levy first trained as a scientist, completing a doctorate in neuroscience. He then continued to medical school, finishing up with a residency in neurology. Lastly, he underwent a two-year fellowship in movement disorders at Columbia, funded by PDF, to specialize in PD research and care. We sat down with him to find out about the life of a physician-scientist and the main goal of his research — slowing Parkinson’s.
Q. How did the PDF-funded fellowship in movement disorders impact your career?
First, it provided me with much-needed clinical training in the care of people with PD. Most neurology residency programs focus on diseases requiring hospital care, such as stroke. Residents often have very limited exposure to diseases treated in the office setting, such as Parkinson’s. Furthermore, the management of PD is complex, given the increasing number of available treatments and the increasing recognition of its breadth of symptoms. The PDF fellowship provided the training I needed to learn about these issues and treat them.
Furthermore, the fellowship provided the opportunity for me to perform valuable research. Basic research (studying the building blocks of PD) requires a significant time commitment — especially at the beginning of one’s career. PDF funding enabled me to spend that time in the lab working on my ideas. I was able to leverage the PDF fellowship training support to secure a much larger grant — a K08 Mentored Career Development Award from the National Institutes of Health — that allows me to advance my PD research even further.
Q. Can you tell us about your research?
In my view, the most critical unmet need in the treatment of PD is the lack of neuroprotective treatments that would slow or stop the progressive loss of neurons — and thus slow or stop the disease. The goal of my research is to identify both the drug targets and the promising candidates for such treatments.
My approach is to start at the most basic level, studying cellular models of PD in the petri dish. In cells, I am looking for pathways that affect neuron loss in PD at a molecular level. My hope is that by studying pathways to Parkinson’s at this level of detail, we can identify specific ways of intervening to slow the disease.
For example, my lab identified a transcription factor called ATF4 (a protein that affects several genes) and found that it helps neurons stay healthy and survive. Because of this, much research has been focused on finding ways of increasing ATF4 levels in order to slow neuron loss (neurodegeneration) in PD.
The good news is that our team has identified a drug called guanabenz that boosts ATF4 levels, thus helping to protect neurons. Guanabenz (Wytensin®)is an exciting drug, because it is already approved by the Food and Drug Administration (FDA) and we know that it can enter the brain (a challenge with PD drugs). This means that if, one day, the drug is proven to work in Parkinson’s, the process of getting it on the market would be quicker and easier than for a brand new drug. Our future studies will test guanabenz and related compounds in animal models of Parkinson’s disease.
Q. How does your dual expertise impact your work in Parkinson’s disease?
In my work as a basic researcher, my clinical training helps me understand which ideas might have the biggest impact on patient care. As a physician, my scientific training offers me a different way of thinking about disease in the clinic. It is exciting to think that what started as research on cells in the lab on ATF4 could one day have an impact on patients.
Dr. Levy’s research has been funded via the PDF Institutional Movement Disorder Fellowship Award and the Research Center Award to Columbia University Medical Center.