A thorough clinical trial with a potential Alzheimer’s drug has failed to prevent or delay cognitive decline, yet another disappointment in the long and difficult search for solutions to this disease.
The year-long trial was the first time that people with a genetic predisposition to develop the disease, but who did not yet show any symptoms, were given a drug designed to stop or slow down the decline in brain function.
The participants were members of an extended family of 6,000 people in Colombia, about 1,200 of whom have a genetic mutation that almost determines that they will develop Alzheimer’s between the ages of 40 and 50.
For many family members living in Medellín and remote mountain villages, the disease quickly robbed them of their ability to work, communicate, and perform basic functions. Many died in the 60s.
In the study, 169 people with the genetic mutation received either placebo or the drug crenezumab, produced by Genentech, part of the Roche group. Another 83 people without the mutation received placebo as a way to protect the identity of people who are likely to develop the disease, which is highly stigmatized in their communities.
The researchers hoped that intervention with a drug several years before memory and thought problems arose could keep the disease at bay and provide important information to deal with 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,” Eric Reiman, executive director of the Banner Alzheimer’s Institute, a research and treatment center in Phoenix, Arizona, and head of the research team, said in an interview. the results.
“Our hearts go out to the families of Colombia and all others who would benefit from effective Alzheimer’s preventive treatment as soon as possible. At the same time, we are pleased to know that this study launched and continues to help shape a new era. in Alzheimer’s prevention research. “
The results are also another setback for drugs targeting a key element of the disease: the amyloid protein, which forms sticky plaques in patients’ brains. Years of studies of different drugs that attack amyloid at different stages of the disease have fallen apart.
In 2019, Roche suspended two other trials of crenezumab, a monoclonal antibody, in humans in the early stages of the more typical Alzheimer’s disease, and said the studies would hardly reveal benefits.
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 acknowledged that it was unclear whether Aduhelm could help patients, but it gave the green light to a program that allows the approval of drugs with uncertain benefits if they are for severe conditions with few treatments and if the drugs affect a biological mechanism with reasonable likelihood of helping patients.
The agency said the biological mechanism was Aduhelm’s ability to attack amyloid, but many Alzheimer’s experts criticized the decision because of the poor results of anti-amyloid therapies. The results of the study, published Thursday, added only the discouraging evidence.
“I wish there was something more positive to say,” said Dr. Sam Gandy, director of the Center for Cognitive Health at Mount Sinai, who was not involved in research in Colombia.
“The pathogenic mutation in the Colombian family is known to be involved in amyloid metabolism,” Gandy said, adding, “The idea was that these were the patients who were most likely to respond to anti-amyloid antibodies.”
The doctor. Pierre Tariot, director of the Banner Alzheimer’s Institute and head of Colombian research, said some of the data suggested that patients receiving crenezumab performed better than those receiving 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 bleeding or swelling in the brain in some patients.
Additional data from the study will be presented at a conference in August. Tariot and Reiman noted that recent findings did not include more detailed information from brain scans or blood tests on the drug’s effect on proteins and other aspects of the biology of Alzheimer’s disease.
They also did not reflect increases in the dose of crenezumab that researchers began giving to 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.
The doctor. Francisco Lopera, a Colombian neurologist and another research leader, began working with family members decades ago and helped establish that their disease was a genetic form of Alzheimer’s. He said the study convinced him that “prevention is the best way to find a solution to Alzheimer’s disease, even if we do not have a good result today.”
Translated by Luiz Roberto M. Gonçalves