Target protein for diabetes drug linked to reduce the risk of Alzheimer’s disease

Researchers from the Karolinska Institutet, Sweden, have discovered that a target protein for a diabetes drug can also help to protect against Alzheimer’s disease. The researchers used genetic methods to study possible candidates to treat the disease. The results of the study, which were recently published in Neurology, highlights that the drug’s target protein could be an interesting candidate for the treatment of Alzheimer’s disease.

“Genetic variants within or nearby the genes that encode a drug’s target proteins can cause physiological changes similar to the effects of the drug,” said the study’s first author Bowen Tang. “We utilise such variants to test the repurposing potential of already approved drugs.”

The researchers began by identifying genetic variants that mimic the pharmacological effect of diabetes drugs, namely lowering blood glucose. This was done through an analysis of data from over 300,000 participants in the UK Biobank register.

The analysis identified variants in two genes that together code for the target protein of a class of diabetes drug called sulphonylureas. The researchers validated these variants by showing their association with, amongst other phenomena, higher insulin release, lower type 2 diabetes risk and higher BMI, which is consistent with the drug’s effects.

The researchers then examined the link between the identified genetic variants and the risk for Alzheimer’s disease. They did this by analysing data collected previously from over 24,000 people with Alzheimer’s disease and 55,000 controls. They found that the genetic variants in the sulphonylurea genes were linked to a lower risk of Alzheimer’s disease.

“Our results suggest that the target protein of sulphonylureas, the KATP channel, may be a therapeutic target for the treatment and prevention of Alzheimer’s disease,” said the study’s last author, Sara Hägg. “This protein is expressed in the pancreas, but also in the brain, and further studies are needed to fully understand the underlying biology.”

The method of analysis applied in the study is called Mendelian randomisation which uses knowledge of genetic variants in individuals as a kind of natural randomisation, not unlike a randomised clinical study. Individuals born with certain protective variants that mimic the effect of a certain drug can therefore be studied for their association to a disease.