The genome of human cells produced in vitro was successfully edited by researchers from the Université Laval Faculty of Medicine and the CHU de Québec–Université Laval Research Centre to introduce a mutation that protects against Alzheimer’s disease. The CRISPR Journal has published the specifics of this breakthrough.
As Professor Jacques-P. Tremblay, the study’s principal author, explains, “Some genetic changes raise the risk of getting Alzheimer’s disease, but there is a mutation that lessens this risk.” “This is an uncommon mutation, discovered in the Icelandic population in 2012.” The mutation has no known negative consequences for those who carry it, and it lowers the chance of Alzheimer’s disease. We were able to modify the genomes of human cells using an upgraded version of the CRISPR gene editing technique.
Those with Alzheimer’s disease have amyloid plaques in their brains, which have a level of toxicity that is thought to induce neuron death. When the amyloid precursor protein is broken by an enzyme called beta-secretase, plaques develop. “The Icelandic mutation makes cleaving the amyloid precursor protein more difficult for this enzyme.” As a result, amyloid plaque development is minimized, “explains Professor Tremblay.
If successful, it could also potentially be used to treat people with the most common form of Alzheimer’s, which occurs after age 65, at the earliest signs of the disease. “The challenge now is to find a way to edit the genomes of millions of brain cells,” says Professor Tremblay. “We are looking at different possibilities, including the use of non-infectious viruses, to deliver the editing complex inside neurons. Now that the proof of concept has been established in human cells in vitro, we will test this approach in mice that express Alzheimer’s disease.
If successful, it might be used to treat people with the most common form of Alzheimer’s, which develops after the age of 65, at the onset of the disease. Professor Tremblay says, “The goal now is to find a mechanism to modify the genome of millions of brain cells.” “We’re looking into a variety of options for delivering the editing complex inside neurons, including the use of non-infectious viruses. In the future, we will test this strategy in mice that express Alzheimer’s disease now that the proof of concept has been produced in human cells in vitro.
If the results are conclusive, we hope to be able to conduct a small-scale study on people with Alzheimer’s disease between the ages of 35 and 40.”Guillaume Tremblay, Jol Rousseau, and Cédric Mbakam are among the authors of the paper published in The CRISPR Journal, in addition to Jacques-P. Tremblay.