Alzheimer's nasal vaccine to enter human trials for the first time, spurring renewed hope for preventing the disease

• Brigham and Women's Hospital is spearheading the first human trial of an Alzheimer's nasal vaccine.
• The vaccine is designed to prevent or slow the progression of the disease.

Alzheimer's treatments seemed like an unlikely prospect just months ago.

Drug trials tried and failed for 20 years to produce treatments that would stop the progression of the disease, and several large pharmaceutical companies abandoned the mission of developing Alzheimer's treatments altogether. So patients' only hopes of improvement were drugs that lessened Alzheimer's symptoms — such as memory loss, insomnia, and loss of language or reasoning skills — for a limited time.

Now, the field of Alzheimer's treatments may finally be opening up.

Last week, Brigham and Women's Hospital announced it would spearhead the first human trial of a nasal vaccine for Alzheimer's, designed to prevent or slow the disease's progression.

The trial is small — 16 people between ages 60 and 85 with Alzheimer's symptoms will receive two doses of the vaccine one week apart. But it builds on decades of research suggesting that stimulating the immune system can help clear out beta-amyloid plaques in the brain. The sticky plaques are a hallmark of Alzheimer's disease. They form when pieces of the beta-amyloid protein accumulate between nerve cells, which could disrupt a person's ability to think or recall information.

The vaccine sprays a drug called Protollin directly into the nasal passage, with the goal of activating immune cells to remove the plaque.

The concept isn't entirely new, but it's particularly promising now that scientists better understand how to treat the disease, Jeffrey Cummings, a brain-science professor at the University of Nevada, Las Vegas, told Insider.

"The idea of activating immune cells is becoming more and more central to the idea of treating Alzheimer's disease," Cummings said. He added that a nasal spray could be better at delivering Protollin to immune cells than an infusion or inhaler.

The trial results could tell us more about how to thwart the disease's progression, since participants must be at an early stage in their illness and otherwise in good health. Before the nasal vaccine can advance to larger trials, though, researchers must demonstrate that it's safe and determine which dose to give.

Approving new Alzheimer's drugs in the wake of controversy

The nasal-vaccine trial comes during a prolific year for Alzheimer's treatments.

In June, the Food and Drug Administration approved the first new Alzheimer's drug in nearly 20 years, an antibody infusion called Aduhelm. But that approval quickly became controversial: Many scientists questioned whether the drug warranted the FDA's green light, since it didn't definitively improve memory or cognition in clinical trials.

Aduhelm was shown to lower the levels of sticky plaque on the brains of Alzheimer's patients, but an FDA advisory committee determined that there wasn't enough evidence to confirm it worked as a treatment. Part of the skepticism stemmed from the fact that the drug's maker, Biogen, discontinued late-stage clinical trials in 2019, as it assumed the drug would fail. Then, roughly six months later, a small group of participants started to show positive results.

"Biogen stopped the trial thinking that it was futile, then followed the patients, and it turned out not to be futile — but, of course, that created a lot of controversy in the interpretation of the data," Cummings said.

The FDA voted to approve the drug under a special accelerated pathway, which green-lights drugs that are likely to benefit patients even when there's uncertainty about how well they work.

Scientists say they've 'turned a corner' on Alzheimer's research

As many as 5.8 million Americans are living with Alzheimer's — a leading cause of death among US adults. Nearly 122,000 Americans died of the disease in 2019, according to the latest available data.

Alzheimer's deaths are also becoming more frequent as more Americans reach old age. From 1999 to 2019, the US mortality rate for Alzheimer's rose 88% — from 16 deaths per 100,000 people to 30 deaths per 100,000 people. That death rate may be an underestimate, since people with cognitive decline sometimes have difficulty seeking an Alzheimer's diagnosis or suffer from other health conditions.

But in the past five years or so, Cummings said, new technologies such as brain scans and blood tests have made it easier to confirm Alzheimer's diagnoses and measure how well treatments are working.

"It just feels like we have turned a corner," Cummings said.

In addition to Aduhelm, he said, a few other antibody drugs have shown promise. The pharmaceutical company Eli Lilly plans to submit data for its Alzheimer's drug, donanemab, to the FDA by the end of the year, which puts it on track for approval in 2022. Two more companies, Biogen and Eisai, are jointly completing an FDA application for their antibody drug, lecanemab.

"These other drugs that are very like" Aduhelm appear to produce a "clinical benefit," Cummings said.

He added: "That's the key: Are patients better, or at least losing their cognitive capacity less rapidly, if they are treated? That seems to be true across this whole class of drugs."