Alzheimer's disease: Promising new treatments!

What are the latest scientific discoveries on Alzheimer's disease?

Currently, there are over 5.7 million Americans living with Alzheimer's disease. It is a neurodegenerative disease characterized by progressive loss of memory and certain cognitive functions. It is a complex, multifactorial pathology caused by the interaction of multiple genetic and non-genetic predisposing factors.

Currently, there is no cure for Alzheimer's disease. Nevertheless, research is making great progress in accelerating the detection and understanding of this pathology...

Because the genetic component is particularly important in Alzheimer's disease, characterizing it is a major challenge for research in order to better understand the mechanisms and be able to propose relevant therapeutic strategies.

Published in the scientific journal Sciences Advances, a 2021 study of nearly 400 brain samples taken after the death of Alzheimer's patients has led to a better understanding of the factors involved in the progression of the disease. Until then, researchers had been studying the disease on laboratory mice, with highly variable results.

Scientists have discovered that the brain of an Alzheimer's patient can already be affected by toxic clusters almost 10 years before the first symptoms appear.

Progressively, neurons are invaded by two types of lesion: Tau protein, which accumulates abnormally, and Amyloid beta, which causes the appearance of so-called "senile" plaques. 

The brain of a person with Alzheimer's disease is smaller than that of a healthy person. The hippocampus, the part of the brain linked to short-term memory, shrinks. Toxic clusters progressively contaminate valid cells, preventing them from functioning properly.

In the course of this study, the scientists realized that it took, on average, 5 years for the toxic clusters to split. Their interpretation of this result is that the neurons are fighting the clusters. This is a much longer time span than that imagined by studying the brains of laboratory mice. And this is encouraging, as it could mean that these 5 years could be used to try and remove the toxic areas. Scientists therefore hope to succeed in delaying the onset of symptoms and degeneration.

These discoveries have led to the development of two new treatments.

What is lecanemab?

A new anti-Alzheimer's medication was approved on January 6, 2023 by the U.S. Food and Drug Administration (FDA): lecanemab, marketed by the Eisai and Biogen laboratories under the name Leqembi. 

This new biotherapy, based on humanized antibodies, is designed to eliminate amyloid peptide protofibrils, thereby slowing the disease's progression. 

This treatment is prescribed to people who have been selected for the Clarity AD clinical trial. These are patients with mild cognitive impairment or at an early stage of the disease. The drug should help slow the progression of symptoms leading to dependence. 

Lecanemab tends to significantly reduce the amyloid burden of treated patients, demonstrating that biotherapy is fulfilling its objective. 

Nevertheless, during the clinical trial, a number of adverse effects were identified in certain patients. These included bleeding (17%) and edema (13%) in the brains of patients. 7% of clinical trial participants had to discontinue treatment due to adverse events. 

Patients taking this new treatment require special monitoring, with regular MRI brain scans.

What is donanemab?

On May 3, 2023, the Lilly laboratory presented positive results from a Phase 3 clinical trial of donamemab, called TRAILBLAZER-ALZ 2. Like lecanemab, this monoclonal antibody against amyloid protein was tested in 1,736 mild Alzheimer's patients aged 60 to 85. These patients had proven cognitive impairment associated with positive amyloid and tau imaging.

Among the participants in this study, 47% of those who received donanemab showed no progression of cognitive decline at 1 year. In comparison, only 29% of the placebo group showed no cognitive decline at 1 year. 

The scientists also measured a 35% slowdown in cognitive decline, which was reflected in the participants' ability to carry out daily activities.

Nevertheless, as with lecanemab, there are significant side effects, including cerebral hemorrhage (ARIA), which remains the most dangerous. There are two types of ARIA: 

• ARIA-E, which occurs at a rate of 24% in treated participants, 
• ARIA-H, with an occurrence rate of 31.4% in clinical trial participants. 

In view of the results obtained in this clinical trial, a submission to the FDA for approval to market the product in the USA will shortly be filed.

>> Find out more about clinical trials in our article! <<

These announcements show that research into treatments for Alzheimer's disease is making significant progress. These results are a source of hope for patients and their families, as well as for doctors around the world.