Alzheimer's brain

What is Alzheimer's?

Alzheimer's is a chronic disease that affects the ability of thinking and destroys the brain of the patient.

A closely monitored clinical trial of a potential Alzheimer's drug has failed to prevent or slow cognitive decline, another disappointment in a long and challenging effort to find a solution to the disease.

Trial of new Alzheimer’s drug

The decade-long study marks the first time someone genetically destined to develop the disease but not yet showing symptoms has been given a drug designed to halt or slow its decline. The participants were members of a large family of 6,000 people in Colombia, about 1,200 of whom had a genetic mutation that almost guaranteed them to develop Alzheimer's disease in their 40s and 50s.

For many family members living in Medellín and remote mountain villages, the disease quickly robs them of the ability to work, communicate and perform essential functions. Many people die in their 60s

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In the study, 169 people with the mutation received either a placebo or crenezumab, a drug made by Roche's Genentech. An additional 83 people without the mutation received a placebo to protect the identities of people who might have contracted the disease, which carries a severe stigma in their communities.

The study's researchers had hoped that using drug intervention in the years before memory and thinking problems were expected to appear could control the disease and provide important insights into addressing more common forms of Alzheimer's that are not caused by mutations in a single gene opinion.

Disappointing Results

"We are disappointed that crenezumab has not shown significant clinical benefit," said Dr. Crenezumab. Eric Reiman, executive director of the Banner Alzheimer's Institute at the Phoenix Research and Treatment Center and leader of the research team, presented the findings in a news release.

"Our hearts go out to the Colombian family and all others who will benefit as soon as possible from effective Alzheimer's prevention treatments. At the same time, we believe this research has begun and will continue to help shape Alzheimer's disease A new era in prevention research."

The result is another setback for drugs targeting a key protein in Alzheimer's disease: amyloid, which forms sticky plaques in the brains of patients with the disease. Years of trials of different drugs targeting amyloid in different disease states have failed. In 2019, Roche stopped two other studies of the monoclonal antibody crenezumab in the more typical early stages of Alzheimer's disease because they showed no benefit.

Last year, in a highly controversial decision, the U.S. Food and Drug Administration approved Aduhelm, an anti-amyloid drug, for the first time.

What did FDA acknowledge about Alzheimer's?

The FDA acknowledged that it was unclear whether Aduhelm could help patients, but gave the green light under a program that allows approval of drugs with uncertain benefits if they are used to treat a few serious diseases and the drugs have an impact on biological Mechanisms that are likely to benefit patients. 

The FDA said the biological mechanism was Aduhelm's ability to target amyloid, but many Alzheimer's experts criticized the decision due to the poor track record of anti-amyloid therapies. Thursday's trial results only added to the disappointing evidence.

"I wish there was a more positive narrative," said Dr. Sam Gandy, director of the Mount Sinai Center for Cognitive Health, who was not involved in the Columbia study.

"It is well known that pathogenic variants in the Columbia family are associated with amyloid metabolism," said Dr. "We think these patients are most likely to respond to anti-amyloid antibodies," added Gandy.

Some data suggest that patients who received crenezumab performed better than those who received a placebo, but the difference was not statistically significant, said Pierre Tariot, Ph.D., director of the Banner Alzheimer's Institute and head of the Columbia study.

He also said there were no safety concerns with the drug, an important finding because many anti-amyloid therapies, including Aduhelm, have caused bleeding or swelling in the brain in some patients.

Additional data from the study will be presented at a meeting in August. Dr. Tariot and Dr. Reiman noted that Thursday's results did not include more detailed information on the effects of the drug on proteins and other aspects of Alzheimer's biology from brain imaging or blood analysis.

Nor did they reflect the increased doses of crenezumab the researchers gave patients as they learned more about the drug. Tario. Some patients received the highest doses for up to two years during the five to eight years of clinical trials, he said.

Prevention is the best solution for Alzheimer's

Francisco Lopera, a Ph.D. Columbia neurologist and another study leader, began working with families decades ago and helped determine that their condition was an inherited form of Alzheimer's . He said the research convinced him that "prevention is the best way to find solutions to Alzheimer's disease."

He said the study convinced him that "prevention is the best way to find solutions to Alzheimer's disease, even if we don't have good results today."

"We know we're taking an important step forward in our contribution to Alzheimer's disease research," he added. "Now we are ready to take further steps to find a solution to this disease."

One participant's wife, Maria Areiza from Medellin, said her husband Hernando was one of the first patients to take part in the study. Hernando, a 45-year-old landline telephone, began experiencing symptoms of cognitive decline about eight years ago. 

He now has Alzheimer's but can still speak. With his decline relatively slow, his family hopes he will benefit from the process.

"I'm very hopeful about this research," his wife said.