Alzheimer's Breakthrough Reverses Disease for First Time

A monoclonal antibody genetically engineered to identify plaque in the brain actually reduces it, doctors report in Nature.

Alzheimer's
Memories don't get 'written' into the long-term memory banks of dementia sufferers. Ayala Tal

Could boosting our own immune systems be the answer to Alzheimer's? A human monoclonal antibody named aducanumab, designed to recognize plaque, seems to actually work, in both mice and men. It's early days and the test sample is small, but the global medical community is agog.

Aducanumab is the first medication to not only slow but actually reverse the buildup of amyloid plaque deposits in the brain associated with the neurodegenerative disease.

Humans to whom the drug is administered saw a significant reduction in brain plaque after a year (54 weeks, actually), while the patients who received placebo experienced no reduction whatsoever, report the scientists in a paper published in Nature. Previous attempts to relieve Alzheimer's using antibody-based immune-system boosters didn't work – but the scientists say they suspect the problems were mainly technical in nature.

Alzheimer's is a progressive dementia condition that affects the elderly. Hallmark symptoms include memory loss, cognitive and behavioral deterioration– and the buildup of proteinaceous deposits called plaques that build up between the nerve cells in the brain, and tangles of nervous cells.

The condition remains impossible to categorically diagnose, let alone cure, before death. In fact, nobody knows for sure what causes these plaques and tangles in the first place. But the more plaques and neurofibrillary tangles there are, the worse the dysfunction is likely to become.

Now a large American and Swiss scientific collaboration, some of whose members work at the drug companies Biogen and Neurimmune, says that administering an antibody designed to recognize and target the plaque, actually reversed its accrual.

The mouse model

First, using genetically engineered mice, the doctors proved that a molecule which is an analog to the antibody aducanumab, applied to a transgenic mouse with Alzheimer's, entered their little brains. The aducanumab analog bound the "bad" protein that forms the plaques and also lowered the protein levels in a dose-dependent manner – the more aducanumab administered, the more the effect.

The human brain (AP)
AP

In short, the molecule crossed the blood-brain barrier, which is a huge obstacle in drug development,"engaged its target", as they put it, and cleared the "bad" protein from plaque-bearing transgenic mouse brains.  

Lovely. Then the scientists applied aducanumab to 165 people diagnosed with prodromal (very early) or mild Alzheimer's, from 2012 to 2014, in the United States.

The treatment with the antibody reduced the plaques in the patients' brains, in a dose and time-dependent manner. The before-and-after images published with the scientists' paper are striking. Some side effects were reported, including headaches.

By the way, everybody develops plaques and tangles in their brains as they age. It is normal. People with Alzheimer's just develop a lot more.

But does the vanishing plaque trick actually improve the patients' behavioral and cognitive problems? The tests were not designed to check that, but the doctors did note that the "cognitive results… provide support for the clinical hypothesis that  reduction of brain plaque confers a clinical benefit." So, apparently, probably, yes. Stay tuned.