Trial of intranasal Alzheimer's vaccine gets underway in US

The first patients are now being treated as part of a first-in-human trial of a vaccine, administered as a nasal spray, that aims to slow down the progression of Alzheimer's disease (AD).

Researchers at Brigham and Women's Hospital in Boston, US, hope that the vaccine will stimulate the immune system to clear the amyloid plaques that are seen in the brains of people with AD and have been linked to the development of dementia.

The human studies follow experiments in mouse models that simulates Alzheimer's, which showed that the vaccine was able to slow down the cognitive impairments that are associated with dementia.

A vaccine delivered by subcutaneous injection targeting tau – a protein which forms tangles that are another feature observed in AD brains – is also being studied by drugmaker Johnson & Johnson in partnership with AC Immune in a phase 1 study. Meanwhile researchers in Japan are also running preclinical studies of an intranasal tau vaccine.

The Boston trial has been more than two decades in development, according to lead investigator Howard Weiner, co-director of the Ann Romney Centre for Neurologic Diseases at Brigham.

"We've amassed preclinical evidence suggesting the potential of this nasal vaccine for AD," he said. "If clinical trials in humans show that the vaccine is safe and effective, this could represent a non-toxic treatment for people with Alzheimer's, and it could also be given early to help prevent Alzheimer's in people at risk."

Clearing amyloid from the brains of people with AD is a longstanding treatment strategy for the disease, and is behind the recent approval of Biogen's antibody drug Aduhelm (aducanumab), but the jury is still out on its value after a lengthy list of failed trials for amyloid-targeting drugs.

Aduhelm itself has proved to be a controversial therapy, with debate still raging about its efficacy and safety, and pushback from clinicians and healthcare payers stalling its rollout.

Earlier this week, the death of a patient treated with the drug refocused attention on the risk of amyloid-related imaging abnormalities (ARIA) with Aduhelm, estimated to occur in around 40% of recipients according to a recent study in the journal JAMA Neurology.

The trial of Brigham's vaccine will eventually enrol 16 people between 60 and 85 years of age with early, symptomatic AD, who will get two administrations of the drug – given one week apart – at a range of doses. Its main objective is gauging the safety and tolerability of the vaccine.

The research team will also measure the effect of nasal Protollin on participants' immune response, including its effects on white blood cells, by examining cell surface markers, gene profiles, and functional assays.

The vaccine is booted using an adjuvant called Protollin, which is already used in some commercial vaccine products and was developed by I-Mab Biopharma and Jiangsu Nhwa Pharmaceutical, which are funding the trial.