Antibody shows promise in slowing cognitive decline in Alzheimer’s

Dr. Steve Salloway, affiliated with Butler and Rhode Island hospitals and The Warren Alpert Medical School, is a co-author of a study showing promising results that may change the face of Alzheimer’s research. / COURTESY DENISE JERUE/BUTLER HOSPITAL
Dr. Steve Salloway, affiliated with Butler and Rhode Island hospitals and The Warren Alpert Medical School, is a co-author of a study showing promising results that may change the face of Alzheimer’s research. / COURTESY DENISE JERUE/BUTLER HOSPITAL

PROVIDENCE – Calling Alzheimer’s disease “the most important public health crisis we face,” Dr. Stephen Salloway, director of neurology and the Memory and Aging Program at Butler Hospital, spoke enthusiastically about a preliminary clinical trial’s impressive results showing “unprecedented amyloid lowering [that], for the first time, seemed to be associated with a slowing of cognitive decline.”

Approximately 165 individuals – 21 of whom were enrolled at Butler Hospital – with some cognitive decline participated in the double-blind trial, where some subjects randomly received aducanumab and others a placebo. Salloway, principal investigator at Butler for this clinical trial, explained that aducanumab is a human antibody that penetrates the brain, binds to the plaque and stimulates the immune system to remove the amyloid plaque. The Alzheimer’s Association calls this amyloid plaque a “prime suspect [along with tangles] in cell death and tissue loss in the Alzheimer brain.

A dozen patients were enrolled in the same aducanumab trial at Rhode Island Hospital, where Dr. Brian Ott, director of The Alzheimer’s Disease & Memory Disorders Clinic, was the principal investigator for a now-completed preliminary trial.
A co-author of the article that appeared in Nature magazine summarizing the trial results, Salloway called those results “encouraging, but preliminary.” Aducanumab – derived by Neurimmune, a Swiss company, which is licensing it to Biogen Inc., in Cambridge, Mass. – will be used in two additional parallel trials with 2,700 subjects. Recruitment of subjects will take another year, followed by 18 months of treatment and then analysis of the data before Biogen can seek approval from the Food and Drug Administration to allow the drug’s commercial manufacture. Both of these phase 3 trials, called confirmatory trials, must show positive results before they are submitted to the FDA, said Salloway. On Sept. 1, Biogen announced that aducanumab received FDA’s fast-track designation, one intended to bring promising drugs for serious conditions to market more rapidly.
While echoing Salloway’s cautious optimism, Ott, who is also a professor of neurology at The Warren Alpert School of Medicine, cautioned, “When you rave about [some drug prospects in clinical trials], some people think that the cure is here, and they want it now. They don’t understand that it’s a gradual process and the drug must go through phases to reach the market.” Although the preliminary trial results showed, depending on the dosage of drug, reduced amyloids in the brain and a slowing of cognitive decline, Ott said that some patients developed edema (swelling) in the brain and others had small hemorrhages in the brain. “That’s why you need to show in phase 3 [with a] large number of people that [the drug is] safe and also works,” he said. “We’re optimistic that we’ll see both those outcomes.”

Only individuals whose positron emission tomography scans test positive for the presence of amyloids are eligible to participate in the trial. Salloway, also a professor of neurology and psychiatry at Brown University’s Alpert Medical School, was one of the researchers who pioneered FDA-approved “tracers” – radioactive dyes that bind to the brain plaques ¬– that now allow researchers to observe plaques in a living person’s brain, when the tracers are used in the PET scan. Before, researchers could only identify those plaques in the brain of an individual, post-mortem.

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‘We’ve treated more than 40 people with this drug; we have more experience than anyone else in the world here at Butler [with aducanumab],” he said. Of the results reported in the Nature article, Salloway added, “This is the best news we’ve had in 25 years … it’s not the finish line but it’s so encouraging.” Both Butler and Rhode Island hospitals are recruiting individuals for the confirmatory phase 3 trial testing aducanumab’s efficacy and safety.

Different Alzheimer’s studies
In other Alzheimer’s news, Butler is also recruiting cognitively normal volunteers, ages 60 to 75, for a five-year Generation Study. Participants in this international study must have two copies – one from each parent – of the APOE4 gene, which puts them at high risk of developing Alzheimer’s, he said. With only two to three percent of the population carrying two copies of that gene, researchers expect to swab the cheeks of 100,000 individuals to identify the 1,300 people needed for the study. A vaccine and an oral medication, both produced by Novartis, will be tested to see if either or both will delay memory loss for individuals at high risk of developing Alzheimer’s. Butler anticipates enrolling 20 to 30 individuals in the Generation Study, a public-private partnership that includes the National Institutes of Health, Banner Alzheimer’s Institute and Novartis, with support from the Alzheimer’s Association.

At Rhode Island Hospital’s Alzheimer’s Disease and Memory Disorders Center, Ott and his team are conducting nine dementia-related clinical trials that range from the Phase 3 confirmatory aducanumab trial to one evaluating the efficacy of yoga as a tool to improve cognition. In addition, Ott is recruiting individuals with mild Alzheimer’s disease for several other upcoming clinical trials, including one sponsored by Eli Lilly and Company, with collaboration from AstraZeneca, and another sponsored by the University of Southern California with several collaborating organizations. In addition, Ott identified the Rhode Island Alzheimer Prevention Registry as “another helpful resource for people interested in participating in Alzheimer prevention research.”

Given the number of people affected, the degree of suffering and the cost of care, Alzheimer’s is a “formidable foe,” said Salloway. Threatening health economies worldwide, Alzheimer’s will require a global effort to prevent it and make it more manageable by delaying the disabilities associated with the disease, he said. In addition to the growing collaborations – rather than competitions – among and between pharmaceutical companies and brain researchers, significant investments of intellect, personnel and money are needed to fight the scourge, though “energizing the public” to get involved is probably the biggest piece needed to solve the Alzheimer’s puzzle, he said.

Contact Rhode Island Hospital at memory@lifespan.org or visit brown.edu/academics/medical/about/departments/neurology/subspeciality-programs/clinical-trials.

Contact Butler’s research line at (401) 455-6402 or visit butler.org/memory.

Contact the Rhode Island Alzheimer Prevention Registry at brown.edu/academics/medical/about/departments/neurology/subspeciality-programs/aging-and-dementia/research/rhode-island-alzheimer-prevention-registry

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