May 6, 2022

It may be possible to improve the lot of patients with Alzheimer’s disease by giving them a drug that attacks the fatty plaques that form in their brains early in the development of the disease, suggests work carried out by Quebec researchers.

Postdoctoral researcher Laura Hamilton, from the CHUM research center, and her colleague Karl Fernandes, associate researcher at the CRCHUM and professor-researcher at the University of Sherbrooke, reported in 2015 that fatty deposits (not to be confused with plaques of proteins better known in the context of Alzheimer’s disease) clogged the brains of patients. These fatty accumulations were first seen in the brains of mice, then their presence was confirmed in human brains during a post-mortem examination. Their new work, which is published in the prestigious scientific journal Nature, is “the second chapter”, said Mr. Fernandes, since they are interested in how we might attack the enzyme responsible for the formation of these lipid deposits. Even more specifically, the new paper focuses specifically on the hippocampus, a brain structure essential for memory and learning.

“What we have seen is that if we give this drug in the (mouse) brain that inhibits the enzyme that creates this fatty acid that we think is toxic, we can knock down a lot of the genes that are involved in Alzheimer’s disease at rates like in wild mice, so (…) at a more normal rate, ”summarized Ms. Hamilton. What’s more, the affected genes play a key role in different facets of Alzheimer’s disease, she added. These fatty deposits appear to form in the brain very early in the course of the disease, long before many other changes that will eventually cause the usual symptoms of Alzheimer’s, but following the buildup of amyloid proteins early in the sickness. “The drug we used will change the composition of fatty acids and it will correct the memory,” said Fernandes. It’s kind of like the missing link between the trigger, the amyloid, and all the things you see followingwards. »

The drug (SCDi) also had the effect of fighting inflammation in the brain and restoring connections between cells, Hamilton said. The mice that received it regained the same memory capacities as a mouse that had never been sick, following only one month of treatment and even if they already showed obvious memory loss. Ms. Hamilton and Mr. Fernandes can almost claim to have been the ones who, as early as 2015, put the scientific community on the trail of these fatty accumulations in the brain in the context of Alzheimer’s disease. But when we go back to the scientific literature, says Mr. Fernandes, we see that Dr. Alois Alzheimer also described these lipid aggregates a hundred years ago. “But following a few years, people kind of didn’t think it was important, so it got forgotten in the literature,” he said.

Anyway, since 2015, several other researchers have been interested in the role that SCDi might play in combating other neurodegenerative diseases, such as Parkinson’s disease and multiple sclerosis. A clinical trial was even initiated in the treatment of Parkinson’s last year. The two Quebec researchers would for the moment be the only ones to examine in depth the role played by these fatty deposits in Alzheimer’s disease. Their work might eventually lead to the development of new tests for the disease and, they hope, new treatments, especially since the necessary inhibitors are already available on the market following being developed for other health conditions. , which will constitute “the third chapter”, said Mr. Fernandes.

“We were able to regulate the memory with a drug, following only one month, underlined Ms. Hamilton. Perhaps if we treat longer, earlier, or later, we might have even more extraordinary effects. We don’t know, but it’s very promising for us. »

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