Diabetes drug target protein linked to reduced risk of Alzheimer’s disease

According to a study conducted by researchers at Karolinska Institutet in Sweden and published in Neurology reports. The results suggest that the drug’s target protein may be an attractive candidate for the treatment of Alzheimer’s disease.

Alzheimer’s disease is becoming more common, but no drug is able to influence the progression of the disease, and the development of new drugs is a slow, expensive and complex process.

Therefore, an alternative strategy is to find already approved drugs that may prove effective against the disease and give them a new field of application. Diabetes drugs have been suggested as potential candidates, but studies that tested diabetes drugs for Alzheimer’s disease have not produced convincing results so far.

In the current study, researchers at Karolinska Institutet used genetic methods to investigate this matter more closely.

“Genetic variants within or near genes that code for drug target proteins can cause physiological changes similar to drug effects,” says first author of the study, Bowen Tang, a doctoral student in the Department of Medical Epidemiology and Biostatistics from Karolinska. Institute. “We are using these variables to test the potential for reuse of already approved drugs.”

The researchers began by identifying genetic variants that mimic the pharmacological effect of diabetes drugs, namely, lowering blood sugar. This was done by analyzing data from more than 300,000 participants in the UK Biobank registry.

The analysis identified variants in two genes that together code for a target protein of a class of diabetes drugs called sulfonylureas. The researchers validated these variables by showing their association, among other phenomena, with increased insulin secretion, a lower risk of type 2 diabetes and a higher body mass index, which is consistent with the drug’s effects.

The researchers then examined the link between specific genetic variants and the risk of Alzheimer’s disease. They did this by analyzing data previously collected from more than 24,000 people with Alzheimer’s disease and 55,000 people in a control group. They found that genetic variants of the sulfonylurea genes were associated with a lower risk of Alzheimer’s disease.

Says the study’s final author, Sarah Hagg, a lecturer in the Department of Medical Epidemiology and Biostatistics Karolinska Institutet. . This protein is expressed in the pancreas, but also in the brain, and more studies are needed to fully understand the basic biology. »

The method of analysis applied in the study is called Mendelian randomization which uses knowledge of genetic variants in individuals as a kind of normal randomization, like a randomized clinical study. Individuals born with certain protective variants that mimic the effect of a particular drug can thus be studied for their association with disease.

The study was funded by the Swedish Research Council, KI-NIH Doctoral Fellowship, Karolinska Institutet, Karolinska Institutet Fellowship for Strategic Research Area in Epidemiology (SFOepi), King Gustaf V Foundation, Queen Victoria Foundation for Freemasons and the National Institutes of Health.

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