While a thorough clinical trial of a potential Alzheimer’s drug has failed to prevent or delay cognitive decline, the long and arduous search for a cure for the disease is another disappointment.
The trial, which lasted for decades, was the first time that people with a genetic predisposition to the disease, but still showed no symptoms, were given drugs designed to stop or reduce brain function.
The participants were members of an extended family of 6,000 people in Colombia, about 1,200 of whom had a genetic mutation that literally determined they would develop Alzheimer’s between the ages of 40 and 50.
For many family members living in Medellin and remote mountain villages, the disease quickly deprived them of the ability to work, communicate, and perform basic tasks. Many died in the 60’s.
In the study, 169 people with genetic mutations were produced by either placebo or the drug Cranzumab, Genentech, part of the Roche group. Another 83 people who did not mutate were given a placebo as a way to protect the identities of people at risk for the disease, which is highly stigmatized in their communities.
Researchers hope that drug interventions before memory and thinking problems appear will help 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.
Eric Ramon, executive director of the Banner Alzheimer’s Institute, a research and treatment center in Phoenix, Arizona, and leader of the research team, said in an interview:
“We pray for families in Colombia and all others who will benefit from effective Alzheimer’s prevention therapy as soon as possible. At the same time, we are pleased to learn that this study has begun and is helping to shape a new era. Alzheimer’s prevention research.”
The effect is even more shocking for drugs that target the main component of the disease: amyloid proteins, which form sticky bands in the patient’s brain. Many years of study of various drugs that attack amyloid at different stages of the disease have failed.
In 2019, Rosh suspended two other trials of cranesumab, a monoclonal antibody, in people in the early stages of more common Alzheimer’s disease, saying the benefits of the study were unlikely to be revealed.
Last year, in a highly controversial decision, the US Food and Drug Administration (FDA) gave the first approval for the anti-amyloid drug Aduhelm.
The FDA acknowledges that it is unclear whether Aduhelm can help patients, but they have given the green light to a program that allows authorization with certain benefits if there are drugs for serious conditions with certain treatments and if the drugs affect the biological system with reasonable potential. To help patients.
The agency said the biological mechanism Aduhelm had the ability to attack amyloid, but the decision was criticized by several Alzheimer’s experts because of its poor track record of amyloid therapy. The results of the study, released on Thursday, only add to the disappointing evidence.
“I want to say something more positive,” he said. Sam Gandhi, director of the Center for Cognitive Health at Mount Sinai, who was not involved in the research in Colombia.
“Pathogenic mutations in the Colombian family are known to be involved in amyloid metabolism,” Gandhi said. “The idea was that these patients respond to anti-amyloid antibodies.”
Physician. Pierre Tarriet, director of the Banner Alzheimer’s Institute and leader of Colombian research, said some data suggested that patients who received cranezumab performed better than patients who received placebo, but the difference was not statistically significant.
He also said that the drug does not have any safety issues, an important finding because many anti-amyloid therapies, including adduhelm, have caused bleeding or brain swelling in some patients.
Additional data from the study will be presented at the conference in August. Tariot and Reiman noted that the latest results do not include more detailed information about the effects of drugs on proteins and other aspects of Alzheimer’s disease biology from brain scans or blood tests.
They also did not show an increase in the dose of cranezumab, which researchers began giving patients when they learned more about the drug, Tariot said. He said some patients took the highest dose for two years out of the five to eight years they participated in the clinical trial.
Physician. Francisco Lopera, a Colombian neurologist and other research leader, began working with family members decades ago to help determine if the disease is a genetic form of Alzheimer’s. He said the study convinced him that “prevention is the best way to find a cure for Alzheimer’s disease, even if our results are not good today.”
Translated by Luiz Roberto M. Gonçalves