New Drug Clears Abnormal Brain Proteins Tied to Alzheimer’s

According to the researchers, animal studies of the drug conducted before the human trial showed the drug to be capable of crossing the blood-brain barrier, engaging its target, and clearing plaques from the brains of mice.

“The findings suggest that aducanumab may slow memory and thinking decline in people with early Alzheimer’s and, although the analysis is only exploratory in this early trial, it paints a positive picture for ongoing trials with the drug”. Aducanumab’s effect in the study participants may be attributed to the antibody’s specific capacity to bond with the abnormally folded amyloid protein fragment.

In preclinical trials with transgenic mice, the global team of scientists (Switzerland and US) showed that a drug similar to aducanumab drastically reduced amyloid plaque build-up. Those trials, begun past year, will include 2,700 participants in North America, Europe and Japan, who will take the drug for 18 months. More amyloid was also removed when people took higher doses of the drug.

Alzheimer’s experts welcomed the results, but cautioned that it is too early to know whether the drug will be a help for patients. In the trial, researchers report the dose and time dependent reduction in the amyloid plaque burden based on PET imaging.

In total, 165 patients received either a placebo or aducanumab for one year.

“Indeed, confirmation that anti-AB (amyloid-beta) treatment slows cognitive decline would be a game-changer for how we understand, treat and prevent Alzheimer’s disease”, commented Eric Reiman at the Banner Alzheimer’s Institute in Phoenix, Arizona.

Yet other tests-including the more in-depth neuropsychological test battery-failed to reveal cognitive differences among treatment groups, said Ronald Petersen, a neurologist at the Mayo Clinic in Rochester, Minnesota, who has consulted for Biogen, but was not involved in this particular project. Although not initially planned as a primary study objective, the good results encouraged researchers to additionally investigate how the treatment affected the symptoms of disease.

The survey of more than 1,500 people found those with dementia are more than twice as likely as the general public to have high rates of loneliness.

Now the team at the University of Zurich has developed an antibody, called Aducanumab, that can bind the harmful plaques together and allow microglial cells to destroy them.

When given to patients once a month for an entire year, the drug can eliminate the plaque buildup in the brain, allowing cellular processes and nerve cell communication to resume. The scientists are now working on ways to avoid the side effect or diminish the problems by reducing the doses patients receive. They found the clumps when analyzing the brains of people who died and suffered from the disease. Of particular interest is p62’s role in the aggregation and degradation of a pair of proteins long recognized as hallmarks of Alzheimer’s disease – tau and amyloid beta.

J. Sevigny et al., “The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease”, Nature, doi:10.1038/nature19323, 2016.

So, if drugs can inhibit the production of the protein in individuals who are at risk of developing the disease, they may be more effective at eliminating the symptoms – and thus the disease over time.

Researchers indicate that the results of the Alzheimer’s disease breakthrough are profound and consistent across the board, even though the initial clinical trial was small in scope.