Hope Grows as Understanding of Alzheimer’s Leads to Bevy of Clinical Studies

Posted in GUMC Stories

JUNE 11, 2015—As director of the Memory Disorders Program at Georgetown University Medical Center, R. Scott Turner, MD, PhD , is haunted by a statistic. If no effective treatment for Alzheimer’s disease is discovered by 2025, the number of affected individuals over age 65 is projected to increase from 5.1 million in 2025 to 13.5 million by 2050.

Progress in treating Alzheimer’s disease has long been stalled — no new drug has been approved for use since 2003, and that drug, memantine, “is better than nothing, but not by much,” Turner said.

But inertia doesn’t describe what is happening with research into, and understanding of, the disorder itself. Turner offered a striking example: “We can now actually see the disease in the brain of a patient while that person is living — before, a diagnosis could only be made with certainty by autopsy.”

“This ability to watch Alzheimer’s in progress — that is, to see the gradual buildup in the brain of tau and beta amyloid proteins linked to the disorder — is a huge benefit in the making and testing of new drugs,” he said. There are already a bevy of agents designed to reduce these proteins in clinical study at Georgetown.

Finding effective therapies can’t come soon enough for Turner, a neurologist who, with his team of four nurse practitioners, sees up to 1,000 patients a year in the Memory Disorders Clinic. Not all have Alzheimer’s, but many do, and others are experiencing mild cognitive impairment (MCI) — often a precursor to Alzheimer’s.

Even with all the energy he puts into caring for his patients, Turner said his efforts are significantly focused on research, “the only way we will ever be able to make a difference in the lives of our patients.”

New optimism

Having the ability to see the progression of Alzheimer’s disease in living patients has given Turner hope. “I believe we are getting to the root causes of Alzheimer’s,” he said. “And I believe we are definitely going to find new and more effective drugs for Alzheimer’s and other disorders of dementia.”

The spring 2015 issue (volume 17) of the Memory Disorders Program newsletter shows the promise of Alzheimer’s research.

It lists six research clinical trials now recruiting patients at Georgetown, but doesn’t make mention of all the studies that are underway, or those that are finished, published or in press.

This level of activity is possible because of the many minds involved in the program — seven clinicians, two faculty researchers, two research assistants, a clinical coordinator, a program coordinator and a regulatory coordinator — all overseen by Turner, the program director.

The sheer number of studies underway makes the Memory Disorders Program the most comprehensive trials program in the greater D.C. area and one of the largest in the country. It is the go-to place in the mid-Atlantic region for a person with Alzheimer’s or with suspected memory issues to engage in clinical study, Turner said.

Patients admitted to these studies will likely receive the best test available today to diagnose Alzheimer’s — a PET brain scan. Turner and his team completed their first tau PET scan in April. And for the past five years, they have used amyloid PET brain scans, which can replace the discomfort of cerebrospinal fluid amyloid tests.

There is a difference between the scans. Beta amyloid clumps and tau protein tangles are hallmarks of the disease, but tau is a much better indication of dementia, Turner said. Researchers know that as cognitive abilities are lost, the trail of dead and dying neurons, clogged with tau tangles, gets longer and longer as it weaves through the brain. The amount of beta amyloid in the brain suggests dementia but does not correlate with cognitive abilities.

These biomarkers of disease — tau, amyloid and spinal fluid — offer both targets for therapy and methods to test if investigation agents work, Turner said. Based on groundbreaking research published by Georgetown researchers last year, fats found in blood can potentially predict mild cognitive impairment. Turner is collecting patients’ blood lipids as part of ongoing clinical trials.

Studies for all…

The studies that Turner conducts enroll patients with Alzheimer’s, MCI and those who are not experiencing any memory loss (for prevention studies and to serve as a comparative control group).

Ongoing clinical trials being conducted with Alzheimer’s patients by Turner and his colleagues are testing anti-amyloid agents and examining a drug to see if it slows decline in early-stage patients.

Others are testing the change in biomarkers over time in patients with Alzheimer’s or MCI or control participants, including one study that is enrolling Vietnam veterans who have had a traumatic brain injury or PTSD, both of which are strong risk factors for development of Alzheimer’s.

And then there are the prevention studies, including the A4 study that opened last year. It is designed for people who are cognitively normal but who have a positive amyloid PET scan. “The scan suggests these folks will probably decline cognitively in the coming years,” Turner said. Some of the patients are being randomized to receive the same anti-amyloid drug also being tested in patients with full-blown Alzheimer’s.

Another prevention trial that Turner pioneered is testing a pharmaceutical-grade synthetic version of resveratrol, found in minute quantities in red wine and grapes. The federally funded study, led by Turner, was held in 21 medical centers across the country. Results of the phase II clinical trial are expected soon.

“Our goal is to be a resource for patients who want to change the course of this devastating illness — not just for themselves, but for our society and our future,” Turner said.

By Renee Twombly
GUMC Communications