Human brain cells could be genetically modified to reduce the risk of Alzheimer's

Brain cells could be genetically modified to reduce the risk of Alzheimer

 

Human brain cells could be genetically modified to reduce the risk of Alzheimer's

A new Canadian study has found that scientists could one day modify human brain cells to prevent the development of Alzheimer's disease. A first step toward proving that engineering a genetic variant in the brain can have the same benefits as inheriting it.

While the causes of Alzheimer's disease are still poorly understood, the prevailing theory so far is that it results from the accumulation of a protein called beta-amyloid outside brain cells. According to the Daily Mail, researchers from Laval University in Canada studied how a key gene in human neurons can reduce the formation of beta-amyloid.

Many variants of this gene increase the production of beta-amyloid, but one variant, called A673T, reduces it. The A673T gene was first discovered in 2012. It is only active in one in 150 people in Scandinavia, but those with it are four times less likely to develop Alzheimer's disease.

Researchers believe that turning on this gene variant in brain cells could reduce the production of beta-amyloid and thus reduce the risk of Alzheimer's disease. According to the team, because the A673T variant only becomes relevant later in life, it has not been selected for by evolution. A673T differs from other variants of the gene by a single DNA letter.

The researchers showed that by editing this DNA letter, the A673T variant can be activated in brain cells growing in a laboratory dish. Professor Jacques Tremblay and his colleagues say this is the first step in proving that engineering the variant into the brain can have the same benefits as inheriting it.

The team is currently working to refine the new technique before testing it on animals. The researchers initially used a CRISPR technique called base editing, which allows for the direct and irreversible conversion of one DNA base to another targeted base.

However, they later turned to a relatively new method called prime editing, a "search and replace" genome editing technique that writes new genetic information directly into the targeted DNA site using a fusion protein. Working with cells in a lab dish, the team was able to modify about 40% of the cells, but they believe a higher percentage may be needed for it to work in the human brain.

Another major issue, the team says, is that by the time people start showing symptoms of Alzheimer's, it may be too late for gene editing to make a difference. But the same is true for any Alzheimer's treatment, according to Dr. Selina Wray of University College London, who was not involved in the research.

Dr. Wray said that all possible treatments, including gene editing, "should be pursued by researchers, as a successful outcome will inevitably be reached eventually." Professor Tremblay said that the modification could be applied to sperm, eggs, or embryos in the future, enabling people with a family history of Alzheimer's disease to be born immune to the A673T variant.