Credit: Longleanna/Pixabay

A research paper published yesterday by Nature online reports that the antibody aducanumab significantly reduced the buildup of protein deposits in the brain that are thought to be a primary cause of the neural degeneration that results in Alzheimer’s disease. The results of the study are very promising and more than warrant further testing on a larger scale. If future clinical trials produce the same results, we may have found a treatment for Alzheimer’s disease.

In an earlier article I explained how protein deposits called beta amyloids accumulate in the brain and how they may lead to Alzheimer’s disease along the following lines. Bacterial pathogens enter the brain from the bloodstream with increasing frequency as the blood-brain barrier weakens with age. The brain combats these pathogens by enclosing them in cages made of proteins called beta amyloids. The caged pathogen dies but the beta amyloid deposit remains. As time goes by, defective tau proteins gather around the beta amyloid deposits and kill surrounding nerve cells. This can lead to inflammation which kills more nerve cells. The loss of these nerve cells is the root cause of Alzheimer’s disease.

The research team attacked protein deposits in the brain with a human monoclonal antibody (an antibody made up of identical clones of single parent cell) called aducanumab that selectively targets beta amyloid. The randomized, double-blind, placebo-controlled study was carried out with 125 patients with early symptoms of Alzheimer’s disease over a two year period. Forty additional patients left the study before completion for various reasons.

The patients were randomly divided into five groups. Each group received 12 monthly infusions of either a placebo or aducanumab at doses of 1, 3, 6 or 10 milligrams per kilogram of body weight. The presence of beta amyloid deposits in the brain was measured before, during and after treatment with molecular PET (positron emission tomography) scans.

The results were striking. Both the duration of treatment and the dosage of aducanumab  reduced beta amyloid deposits. After 12 months of treatment, the patients that received the largest dose of aducanumab had PET scans that showed only minor differences from scans of people who show no evidence of Alzheimer’s disease.

The study was designed to test whether aducanumab reduces beta amyloid deposits in humans and whether increasing doses of the antibody are both safe and tolerable. The study wasn’t designed to test whether aducanumab mitigated Alzheimer’s symptoms as measured by clinical tests. Nevertheless, clinical tests were carried out with mixed results. The evidence of a reduction of Alzheimer’s symptoms on some clinical tests motivates further testing that has the statistical power to examine outcomes on both brain imaging and clinical measures.

Treatment with aducanumab had side effects including ARIA-E, headache, urinary tract infection and upper respiratory tract infection. ARIA-E is a type of fluid buildup that has been shown to follow monoclonal antibody attacks on beta amyloid deposits. In the study, ARIA-E increased as the dosage of aducanumab increased. The fluid buildup occurred during the early stages of treatment and dissipated within four to 12 weeks.

The small sample sizes and limitation to patients in the United States mean that it’s far too early to begin talking about aducanumab as a possible cure for Alzheimer’s disease. However, as the author’s of the study point out, beta amyloid deposits that may have taken 20 years to accumulate were significantly reduced, and in the case of those receiving the highest dose of aducanumab virtually eliminated, after only 12 months of treatment. This research is very promising and more powerful clinical trials are underway.