A closely watched clinical trial of a potential Alzheimer’s drug has failed to prevent or slow cognitive decline, another frustration in a long and challenging effort to find out. solution to this disease.
The decades of testing is the first time people who are genetically destined to develop the disease – but have not yet shown any symptoms – are given a drug intended to halt or delay the decline. The participants were member of an extended family out of 6,000 people in Colombia, about 1,200 of them have a gene mutation virtually guarantees that they will develop Alzheimer’s disease between the ages of 40 and mid 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 people die in their 60s.
In the trial, 169 people with the mutation received either a placebo or the drug, crenezumab, Produced by Genentech, part of the Roche Group. Another 83 people without the mutation received a placebo as a way to protect the identities of those likely to develop the disease, which is highly stigmatized in their communities.
The trial investigators had hoped that drug intervention years before memory and thinking problems appeared could halt the disease and provide important insights into tackling the disease. Alzheimer’s is more common without a single gene mutation.
Dr Eric Reiman, executive director of the Banner Alzheimer’s Institute, a research and treatment center in Phoenix, and lead researcher, said: “We are very disappointed that crenezumab has not shown any clinical benefit. substantial availability. about results. “Our hearts go out to the families in Colombia and to all others who will benefit from an effective Alzheimer’s prevention therapy as soon as possible. At the same time, we take to heart the knowledge this study provides and continue to help shape a new era in Alzheimer’s prevention research. ”
The results are also another hurdle for drugs that target a key protein in Alzheimer’s disease: amyloid, which forms sticky plaques in the brains of patients with the disease. Years of research with multiple drugs that attack amyloid in different stages of the disease have failed. In 2019, Roche pauses two more trials of crenezumaba monoclonal antibody that, in people in the early stages of more typical Alzheimer’s disease, says studies have shown no benefit.
Last year, in a controversial decision, the Food and Drug Administration licensed the first anti-amyloid drug, Aduhelm. The FDA admits it’s unclear whether Aduhelm can help patients, but has revealed it is under a program that allows the licensing of drugs with uncertain benefit if they’re intended for serious illnesses with few treatments. treatment and if the drug affects a biological mechanism that is reasonably likely to help. patient. The FDA attributed the biological mechanism to Aduhelm’s ability to attack amyloid, but many Alzheimer’s experts criticized the decision because of the poor performance of anti-amyloid therapies. Thursday’s trial results only add to the disappointing evidence.
“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 Colombian study.
Dr Gandy adds: “The pathogenic mutation in the Colombian family is known to be involved in amyloid metabolism.
Dr. Pierre Tariot, director of the Banner Alzheimer’s Institute and leader of the Colombian research team, said some data showed that patients taking crenezumab were better off than patients taking placebo, but the difference was not statistically significant. .
He also said there were no safety issues with the drug, an important finding because many anti-amyloid therapies, including Aduhelmhas caused brain bleeding or swelling in some patients.
Additional data from the trial will be presented at a conference in August. Drs Tariot and Dr Reiman note that Thursday’s results do not include more detailed information from brain imaging or blood analysis. on the effects of drugs on protein and other aspects of the biology of Alzheimer’s disease. They also don’t reflect the increase in the dose of crenezumab that researchers started giving patients as they learned more about the drug, Dr. Tariot said. He said some patients received up to two years of the highest dose within the five to eight years they were in the clinical trial.
Dr. Francisco Lopera, a Colombian neuroscientist and another leader of the study, began working with family members decades ago and helped determine that their pain was an inherited form of Alzheimer’s disease. He said the trial convinced him that “prevention is the best way to find a solution for Alzheimer’s, even if we don’t have good results today.”
He added: “We know that we have contributed an important step towards the investigation of Alzheimer’s disease. “And now we are about to begin other steps towards finding a solution to this disease.”
One participant’s wife, Maria Areiza of Medellín, said her husband, Hernando, whose last name was kept secret to protect his privacy, was one of the first patients to sign up for the trial. Hernando, 45, a telephone cable repairman, began developing symptoms of cognitive decline about eight years ago. He has progressed to Alzheimer’s disease but can still talk. Because of his relatively slow decline, his family had hoped that he would benefit from the trial.
“I put all my hopes into this study,” his wife said.
Jennie Erin Smith contributed reporting from Medellín, Colombia.
