By NORBERT HERZOG and DAVID NIESEL
More than 5 million Americans are currently living with Alzheimer’s disease, the sixth leading cause of death. Unfortunately, a comprehensive review found that four Alzheimer’s drugs had short-term benefits that are lost after a year and a half of treatment. However, there is some hope in a new drug called aducanumab, which sharply reduced cognitive decline in patients with early symptoms of dementia in a small clinical trial.
Dementia is a neurological condition with a broad range of symptoms that interfere with a person’s ability to perform daily functions. It is diagnosed when there are significant impairments in memory, communication, language, judgment, reasoning, visual perception and the ability to focus or pay attention. It is usually progressive, so patients steadily lose their cognitive abilities and require increasing levels of care. Patients diagnosed with Alzheimer’s, which accounts for about 60-80 percent of dementias, live an average of eight to 10 years after their symptoms begin.
Scientists do not yet know what causes Alzheimer’s, but it is likely a complex series of events over a long period of time. The brains of people with Alzheimer’s have three abnormal features. Amyloid plaques and neurofibrillary tangles are made up of proteins that are misfolded and aggregate, disrupting normal brain functions. The third feature, reduced connections between brain cells, eventually causes them to die and the brain to shrink.
The new drug, aducanumab, was used in a Phase I clinical trial to determine its safety, not its efficacy, but the results were a pleasant surprise. One problem with Alzheimer’s drugs is that they are often prescribed too late in the disease, but with new imaging technology that can determine the accumulation of plaque, patients with the potential to develop dementia can be identified earlier. This study enrolled 166 patients in the early stages of dementia with plaques in their brains. They were randomly assigned to receive aducanumab or a placebo. Aducanumab targets an amyloid protein that causes plaques in the brain and triggers an immune response to eliminate it. It worked, substantially reducing plaque and slowing cognitive decline by 70 percent as measured by two different tests.
A major side effect was localized swelling of the brain, which occurred in 55 percent of subjects with the version of a gene that puts them at a higher risk of Alzheimer’s and 17 percent of those without it, prompting several to drop out of the study. Such swelling can occur naturally in Alzheimer’s patients, so the drug may just hasten its development, but it can be diagnosed, monitored and controlled by changing the dosage.
Overall, the results are very encouraging, although other Alzheimer’s drugs that were later found to have no effect on disease progression in large trials also had promising results early on. We remain cautiously optimistic that this new drug will be effective in subsequent clinical trials and that side effects can be minimized.
Professors Norbert Herzog and David Niesel are biomedical scientists at the University of Texas Medical Branch. Learn more at medicaldiscoverynews.com.