Recent failures in much-anticipated drug trials to treat Alzheimer’s disease represent — yet again — a disappointing setback in the quest for a cure.
One trial failed to demonstrate clinical effect in using specifically designed antibodies to clear the amyloid from the brain. Similarly, another recent trial did not demonstrate effectiveness in symptomatic patients when it targeted the enzyme that is essential in pathologic amyloid production. These results were very disappointing to the patients, their families, and providers involved in their care, and they have left many understandably questioning if the scientific community is moving in the right direction when it comes to tackling this disease.
Developing an effective treatment for dementia is more urgent than ever, particularly in our region. Approximately 400,000 Pennsylvanians are affected by Alzheimer’s or a related disorder, including 57,000 in Philadelphia, and 85,000 in South Jersey, according to the Alzheimer’s Association.
Amyloid accumulation is currently considered to be one of the main players driving development of the disease. Most of the Alzheimer’s drugs in clinical trials are designed to reduce the buildup of these plaques, which are thought to contribute to memory loss. The results of these clinical trials now bring into question whether there is any real relationship between amyloid deposition and cognitive problems.
While the question is fair, one important point is being overlooked: The trials that failed were conducted on patients who already had symptoms from the disease, specifically memory impairment.
Current scientific data support the hypothesis that amyloid plaques start accumulating in the brain at least a decade before the first symptom of dementia arises. In other words, people harbor amyloid for many years, and it is becoming clear that by the time the first symptom surfaces, some of the changes in the brain may not be reversible.
A solution may be to start the interventions earlier, before symptoms appear. In the advent of Alzheimer’s disease biomarker studies, we are able to identify asymptomatic people who have amyloid in their brain by using a special brain scan (called amyloid PET scan) or through analyzing cerebrospinal fluid. These significant developments allow us to look into the disease before it manifests.
Right here in Philadelphia, researchers are already using these methods to address the disease at the earliest stage possible. The study (or “A4,” for short) is a national clinical study that is trying to identify people without any cognitive impairment who have pathologic amyloid present in their brain.
If the person meets certain criteria, then they are welcomed to join the study. Upon enrollment, they start receiving monthly treatment with specific antibodies to clear the amyloid from the brain. This will help to determine whether clearance of amyloid from the brain before cognitive symptoms start occurring can prevent or stall the disease from developing into significant cognitive impairment.
The importance of this study cannot be stressed enough, as its results could reshape the way we approach and treat this disease. If successful, then we will know that decreasing amyloid with antibody treatment can help slow memory loss associated with amyloid buildup. If they do not show the results we are hoping for, then it may be time to start testing a new hypothesis and trying new approaches, rather than continuing to tackle amyloid.
We are also hopeful that treating patients with very early symptoms of memory loss could slow the progression of Alzheimer’s disease. While the results of failed trials suggest that studies targeting moderate to severe Alzheimer’s attempted to intervene too late, there are studies looking for individuals with prodromal to mild Alzheimer’s. Some of these studies are using different antibodies to remove pathological amyloid (such as the CREAD trial), while others are trying to affect the enzyme involved in its production (AMARANTH, APECS trials). What is vital is that we address the disease as early as possible.
So now is not the time to lose hope. We are moving toward a deeper understanding of Alzheimer’s — but only with the public’s help. The medical community is pleading for people to get involved in clinical trials in order to move fast in ending this disease.
The Neurosciences Institute at Drexel University College of Medicine is currently enrolling for various Alzheimer’s disease prevention and treatment clinical trials. Interested volunteers -- participants in the A4 study should be between ages 65 and 85 -- should contact Katie Rife at 215-762-6915 or email@example.com.
Peter Gliebus, M.D., is director of the Cognitive Disorders Center at Drexel University College of Medicine. He can be reached at firstname.lastname@example.org.