Human Brain Cells Gene-edited To reduce The Risk Of Developing Alzheimer’s Disease
Cells in the human brain could one day be edited by scientists to prevent the development of Alzheimer’s disease, a new study suggests. The causes of Alzheimer’s are still not well understood, but a leading theory is that it is triggered by the build-up of a protein called beta-amyloid outside the brain cells. Researchers from Laval University in Canada have been investigating how a key gene in human nerve cells could reduce the formation of this protein. Many variants of this gene increases beta-amyloid production, but one variant, called A673T, instead reduces it.
A673T was first discovered in 2012, and is only active in one in 150 people in Scandinavia, but those that have it are four times less likely to get Alzheimer’s. The researchers believe that switching on this gene variant in brain cells could reduce the production of beta-amyloid and thereby reduce Alzheimer’s risk. As the A673T variant doesn’t become relevant until later in life, it isn’t selected for by evolution, according to the study authors. It differs from other variants of the gene by a single DNA letter. Researchers showed that, by editing this one DNA letter, they were able to activate the A673T variant in brain cells growing in a culture dish. Jacques Tremblay and colleagues say this is the first step to proving that engineering the variant into brains could have the same benefits as inheriting it.
The team are still refining the technique before they try it on animals. The researchers initially used a CRISPR technique called base editing, which allows the direct, irreversible conversion of a DNA base into another, targeted base. However, they have now switched to a relatively new method called prime editing – a ‘search and replace‘ technique for editing genomes that directly writes new genetic information into a targeted DNA site using a fusion protein. Working with cells in a dish they managed to edit about 40 per cent of the cells, but they think a higher proportion might be needed for it to work in a human brain.
The researchers worked with a process known as base editing, a relatively new method that allows the direct, irreversible conversion of a DNA base into another, targeted base