A class of Alzheimer’s drugs, including the promising lecanemab, could cause the brain to shrink, according to a study by researchers at the Florey Institute of Neuroscience and Mental Health in Melbourne, Australia.
Lecanemab is an Eisai and Biogen treatment in the investigational phase which is considered one of the most promising against the treatment of mild cognitive impairment (MCI) in the early stages of Alzheimer’s.
Since January 6, it has the expedited approval in the United Statesalthough it must be ratified in July, and also since that month the European Medicines Agency (EMA) is reviewing its authorization.
The drug reduces cognitive impairment by 27%
Clinical trials conducted so far have shown that the drug reduces by 27 percent the Mild cognitive impairment in people with Alzheimer’s after 18 months of treatment. In addition, it also decreased levels of amyloid in the brain, one of the key proteins in the disease.
Doubts about your safety
However, some experts have shown some doubts about the safety of the drug in certain patients. In November, the scientific journal ‘Science’ described the death of a trial volunteer due to a massive cerebral hemorrhage, the second produced in the study with lecanemab.
The woman suffered a stroke and was treated with an anticoagulant, which caused bleeding. She also had cerebral amyloid angiopathy (CAA), a disease in which the smooth muscle in the blood vessel walls of the brain is gradually replaced by deposits of amyloid.
weakens blood vessels
Lecanemab targets amyloid, and according to AAC experts, its use likely weakened the woman’s blood vessels, triggering bleeding. Although it can be difficult to diagnose before death, even with brain scans, CAA occurs in about half of Alzheimer’s patients, so “it could be dangerous to administer lecanemab without firm warnings about its apparent interaction with anticoagulants”as warned by the American Association for the Advancement of Science.
Another study that questions lecanemab
Now, this new research, published in the scientific journal ‘Neurology’, has analyzed 31 clinical trials that have shown changes in brain volume with different types of anti-amyloid drugs against Alzheimer’s. He also links brain shrinkage to a better-known side effect of drugs, cerebral edema, which often has no symptoms.
Specifically, the study points to secretase inhibitors (which have failed in clinical trials and worsened cognition) and monoclonal antibodies, including some of the latest, best-known drugs against the disease: aducanumab, lecanemab, and donanemab (rejected in the EE .UU. in January).
Aducanumab, marketed as ‘Aduhelm’, was approved in the United States in 2021 despite doubts about its effectiveness and safety. The EMA rejected its approval in Europe, considering that “scientific evidence does not sufficiently demonstrate that it is effective for treatment in adults in the early stages.” Following these decisions and with growing doubts about the drug, Biogen announced in May 2022 that it was leaving its marketing.
28% less brain volume
According to this new review of studies, participants in two large trials of lecanemab at the highest dose of the drug, which is the one approved in the United States, registered on average a 28 percent greater loss of brain volume in relation to placebo after 18 months.
The authors have also verified that antibodies such as lecanemab caused an increase in the size of the cerebral ventricles, indicating that they were filling with fluid. Specifically, in people who received the approved dose of lecanemab, their size increased 36 percent more than in those who took placebo.
“Monoclonal antibodies caused about a 40 percent acceleration in lateral ventricular enlargement, which is a classic marker of neurodegeneration. This was only seen with drugs that induced amyloid-related imaging abnormalities (ARIAs), and we found a striking correlation between the ARIA rate and the degree of ventricular volume enlargement,” study leader Scott Ayton told MedPage Today.
When the study results were published in November, Raquel Sánchez-Valle, Head of the Neurology Service at Hospital Clínic de Barcelona, already pointed out that 21.5 percent of those treated with lecanemab presented some of the alterations in magnetic resonance imaging that have been related to ARIA, compared to 9.5 percent in the placebo arm.
For its part, Eisai, the company behind the drug, has told ‘Science’ that there are also theories that brain shrinkage could be positive. Specifically, he has argued that although participants in his pivotal trial experienced “greater cortical volume loss with lecanemab than with placebo,” those reductions may be due to the antibody clearing amyloid protein from the brain and reducing inflammation.