Alzheimer's Disease May Be Prevented by Blocking Gene

Monday, April 16, 2018

Alzheimer's Disease May Be Prevented by Blocking Gene

Using human brain cells, scientists have discovered the cause of—and a potential solution for—the primary genetic risk factor for Alzheimer’s disease, a gene called ApoE4.

Scientists have neutralized the most significant gene responsible for Alzheimer's Disease for the first time. The study could be a bridge to a potential new drug capable of halting the disease. The  researchers have urged caution though,  because so far their compound has only been tried on collections of cells in a laboratory.

The research team, based in California, successfully identified the protein associated with the high-risk apoE4 gene and then managed to prevent it damaging nearby brain cells. The study appears in the journal Nature Medicine.

ApoE4 protein
The gene ApoE4  has been found to cause neuronal degeneration, a major factor in Alzheimer's disease

In our brains, the misshapen apoE4 protein cannot function properly and is broken down into disease-causing fragments in the cells. This results in several of the problems commonly found in Alzheimer’s disease, including the accumulation of protein tau and amyloid peptides.

Having one copy of the apoE4 gene more than doubles a person’s likelihood of developing Alzheimer’s disease, whereas having two copies increases the risk 12-fold.

Previous studies have indicated that roughly one in four people carry the apoE4 gene.

For the research, a team at Gladstones Institutes tried to establish whether the presence of the protein was causing the damage, or whether a lack of it was to blame. Using regenerative medicine technology, they created neuronal stem cells from skin cells donated by Alzheimer’s patients with two copies of the apoE4 gene.

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By comparing the cells with those which did not produce an apoE protein they concluded that it was the the mere presence of the apoE4 protein was causing brain damage.

They then applied a genetic “structure corrector”, which eliminated the signs of Alzheimer’s.

The researchers are now working with the pharmaceutical industry to improve the compounds so they can be tested on human patients.

The experiment is particularly significant because it took place in human cells.

“Drug development for Alzheimer’s disease has been largely a disappointment over the past 10 years,” says lead author Yadong Huang, MD, PhD, a senior investigator and director of the Center for Translational Advancement at Gladstone.

“Many drugs work beautifully in a mouse model, but so far they’ve all failed in clinical trials. One concern within the field has been how poorly these mouse models really mimic human disease.” Huang and his colleagues went straight for human brain cells rather than the traditional mouse trial because they realised the presence of the apoE4 gene does not change the production of amyloid beta in a mouse brain.

Huang and his team are now working with his collaborators in academia and the pharmaceutical industry to improve the compounds so they can be tested in human patients in the future.

SOURCE  Gladstone Institutes

By  33rd Square