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Faculty Spotlight: James Burke, MD, PhD

Tuesday, January 9, 2018

After decades of research and more than 100 experimental medications, there is still no effective medication for Alzheimer’s disease. James Burke, MD, PhD, hopes to change this. In this week’s Faculty Spotlight interview, Burke reflects on what we’ve learned about this and related conditions during his three decades at Duke, how our understanding of the condition may change over the next decade, and why the most effective approach to the condition may be like changing the course of an ocean liner.

What are your responsibilities within the Neurology Department? What does your average work day look like?
I am the division chief for Behavioral Neurology and an IRB board member. I spend about 40% of my time seeing memory disorders patients and the remainder working on clinical trials and the IRB.

What drew you to neurology? What led you to focus on Alzheimer’s disease and dementia in particular?
I have always been interested in the biological process of aging. I have a PhD in Biochemistry from Oak Ridge National Laboratory Graduate School of Biomedical Sciences where my thesis dissertation explored the fidelity of protein synthesis in aging. As a young faculty member I worked with Allen Roses, Margaret Pericak-Vance, and Jeffrey Vance on the genetics of neurodegenerative diseases and identified the gene causing a rare form of dementia called Haw River syndrome. At about the same time, Allen Roses, Margaret Pericak-Vance, and Warren Strittmatter of our Division of Neurology discovered that APOE was the major genetic risk factor for late-onset Alzheimer’s disease and it seemed obvious that focusing on AD was the right choice for me.

What do you enjoy most about your work? What’s the hardest part of your job?
I enjoy working on developing new therapies for Alzheimer’s disease. The time frame for bringing a new drug to market is measured in decades, but it is critical work. The hardest part of my job is realizing that after over 30 years in the Memory Disorders Clinic we still do not have a disease-modifying therapy.

Your research focuses on characterizing cognitive change that occurs during aging. What specific projects are you working on at the moment?
My main focus is clinical trials to delay onset of Alzheimer’s disease. Experience has shown that finding drugs that treat patients who already have dementia is extremely difficult. More than 100 drugs have been tried with no successes. The consensus of the field is that treating people before they have symptoms may be more successful. One analogy is that with Alzheimer’s we are trying to turn an ocean liner. Small corrections earlier in the course result in larger changes than trying to turn the ship on a dime.

To find patients at risk of developing Alzheimer’s who currently have no symptoms we use two approaches. One approach is to use genetics, especially APOE and another gene polymorphism discovered at Duke called TOMM40, and the other is to identify people who have biomarkers of Alzheimer’s in their brain or spinal fluid. The drugs currently being studied are an insulin-sensitizing medication, a vaccine against amyloid, and inhibitors of an enzyme responsible for making the toxic form of amyloid that accumulates in the brains of people with AD. I am also working with a wide range of investigators on projects that examine the retinal vasculature in dementia, the effect of chronic pesticide exposure on developing dementia, the use of amyloid imaging in clinical practice, and the psychological and cognitive effects of patients being informed about their amyloid status.

How has our understanding of the changes that occur during aging, especially those that occur with dementia and Alzheimer’s disease, changed over the past 30 years?

Our understanding of AD has changed dramatically. We now know that the pathologic changes of AD begin decades before the first symptoms develop. This gives us hope that intervening earlier in the disease process may be successful. On the flip side, we also recognize that a significant number of older people have pathologic signs of AD, but have no symptoms. So, we clearly do not understand the whole picture.

What advances in this area do you see coming over the next decade?
A number of clinical trials will be completed in the next decade which will inform us about whether intervening earlier in the disease process is successful. I also expect that we will have more effective treatments for the behavioral problems associated with dementia.

What passions or hobbies do you have outside of the Department?
I love to read, especially novels. I am currently working my way through the novels of John Banville, who also writes a mystery series under the pseudonym Benjamin Black. The flawed hero of the crime series is an alcoholic pathologist named Quirke.