HEALTH. Researchers from Laval University and the CHU de Québec Research Center are studying a new protection against Alzheimer’s disease. They achieved this by introducing a mutation into the genome of human cells cultured in vitro. Details of this breakthrough have just been published in The CRISPR Journal.
“Certain genetic mutations increase the risk of developing Alzheimer’s, but there is one mutation that reduces this risk. This is a rare mutation identified in 2012 in the Icelandic population. This mutation has no known disadvantages for people who carry it and it reduces the risk of suffering from the disease. Thanks to an improved version of the CRISPR genome editing tool, we managed to edit the genome of human cells to insert this mutation,” explains Professor Jacques-P. Tremblay responsible for the study.
We know that the brain of people with Alzheimer’s has amyloid plaques whose toxicity would cause the death of neurons. These plaques are formed when the amyloid precursor protein is broken down by an enzyme called beta-secretase. “The Icelandic mutation causes the amyloid precursor protein to be less easily cleaved by this enzyme. Consequently, the formation of amyloid plaques is reduced”, specifies Professor Tremblay.
Irreparable losses
In theory, introducing the Icelandic mutation into the genome of people at risk could prevent or slow down the disease. On the other hand, we cannot go back and repair the damage that caused the death of neurons. The treatment would therefore be indicated for people affected by the hereditary form of Alzheimer’s, which manifests itself in memory problems from the age of 35 to 40 years. If this therapy works well, it could also be considered to treat people with the most common form of the disease, which manifests after age 65.
The challenge now is to find a way to edit the genome of millions of brain cells. “We are investigating different possibilities, including the use of non-infectious viruses, to deliver the editing complex inside neurons. Now that the proof of concept has been done on human cells in vitro, we are going to test this approach in mice,” says Jacques-P. Tremblay, speaking on behalf of fellow researchers Guillaume Tremblay, Joël Rousseau and Cédric Mbakam.