An extensive clinical trial of a potential drug for Alzheimer’s have failed to prevent or delay cognitive decline, yet another disappointment in the long and difficult search for solutions to this disease.
The decade-long trial was the first time people with a genetic predisposition to develop the disease, but not yet showing symptoms, were given a drug designed to halt or slow the decline in brain function.
The participants were members of an extended family of 6,000 people in Colombia, of whom approximately 1,200 have a genetic mutation that virtually determines that will develop Alzheimer’s disease between the ages of 40 and 50.
For many family members, who live in Medellín and remote mountain villages, the disease quickly robbed them of their ability to work, communicate and perform basic functions. Many died in their 60s.
In the study, 169 people with the genetic mutation were given either a placebo or the drug crenezumab, produced by Genentech, part of the Roche group. Another 83 people without the mutation were given the placebo to protect the identity of people at risk of developing the disease, which is heavily stigmatized in their communities.
Researchers hoped that drug intervention years before the onset of memory and thinking problems could control the disease and provide important information for treating the most common type of Alzheimer’s, which is not caused by a single genetic mutation.
“We are disappointed that crenezumab did not have a significant clinical benefit,” said Eric Reiman, executive director of Banner Alzheimer’s Institute, a research and treatment center in Phoenix, Arizona (United States), and leader of the research team, during a press conference on the results.
“Our hearts go out to the Colombian families and all others who would benefit as soon as possible from an effective preventive therapy against Alzheimer’s disease. At the same time, we are delighted to know that this study has launched and continues to help shape a new era. Research on the prevention of Alzheimer’s disease.”
The findings are also another setback for drugs that target a key component of the disease: the amyloid protein, which forms sticky plaques in patients’ brains. Years of studies on various drugs that attack amyloid at different stages of the disease have crumbled.
In 2019, Roche suspended two more trials of the monoclonal antibody crenezumab in people in the early stages of more typical Alzheimer’s disease, saying the studies were unlikely to show benefit.
Last year, in a highly controversial decision, the US Food and Drug Administration (FDA) granted its first approval for an anti-amyloid drug, Aduhelm.
The FDA has acknowledged that it’s unclear if Aduhelm can help patients, but it has given the green light to a program that allows drugs of uncertain benefit to be approved if they’re for serious conditions with little of treatments and whether the drugs affect a biological mechanism with a reasonable probability. .to help patients.
The agency said the biological mechanism was Aduhelm’s ability to attack amyloid, but many Alzheimer’s disease experts criticized the decision because of the poor track record of anti-amyloid therapies. The results of the study, released on Thursday, only added to the dismal evidence.
“I wish there was something more positive to say,” said Dr. Sam Gandy, director of the Mount Sinai Center for Cognitive Health, who was not involved in the Colombia research.
“The pathogenic mutation in the Colombian family is known to be involved in amyloid metabolism,” Gandy said, adding, “The idea was that these are the patients most likely to respond to anti-amyloid antibodies.”
Doctor. Pierre Tariot, director of the Banner Alzheimer’s Institute and a leader in Colombian research, said some of the data suggested that patients who received crenezumab fared better than those who received the placebo, but the differences were not statistically significant.
He also said there were no safety issues with the drug, an important finding because many anti-amyloid therapies, including Aduhelm, have caused brain bleeding or swelling in some patients.
Additional data from the study will be presented at a conference in August. Tariot and Reiman noted that the latest results did not include more detailed information from brain scans or blood tests about the drug’s effects on proteins and other aspects of Alzheimer’s biology.
They also did not reflect increases in the dose of crenezumab, which researchers began giving patients as they learned more about the drug, Tariot said. He said some patients received the highest dose for up to two years out of the five to eight years they participated in the clinical trial.
Doctor. Francisco Lopera, a Colombian neurologist and another research leader, began working with family members decades ago and helped determine that their condition was a genetic form of Alzheimer’s disease. He said the study convinced him that “prevention is the best way to find a solution to Alzheimer’s disease, even if we don’t have a good result today”.
Translated by Luiz Roberto M. Gonçalves