It is not known when clinical trials with gemfibrosil and retinoic acid might begin. (Photo: The Canadian Press)

Two molecules known and available for a long time offer new hope for combating Alzheimer’s disease, in particular with regard to the destruction of the tangles of proteins which characterize the disease.

Gemfibrosil was previously used for high cholesterol, but has lost popularity in favor of statins. The other substance, retinoic acid, is a derivative of vitamin A that can fight certain skin problems. Each product had previously been studied separately for Alzheimer’s.

Researchers at the University of Chicago found that the two molecules appear to have an effect on astrocytes, cells that may be responsible for the protein plaques that build up in the brains of patients with Alzheimer’s disease.

Used together, gemfibrosil and retinoic acid could one day instead reverse the role of astrocytes by causing them to clean up these protein tangles, which could prevent some of the disease’s worst ravages.

“The same team had shown (…) that gemfibrosil reduced amyloid plaques in the brain and even that it improved spatial memory in mice,” said Professor Charles Ramassamy, a specialist in Alzheimer’s disease at the National Institute of Scientific Research.

This time, he continues, by combining the two molecules, the researchers observed a decrease in amyloid plaques in the brains of animals and a reduction in the proliferation of certain cells that are involved in neuroinflammation.

It is not known when clinical trials with gemfibrosil and retinoic acid might begin.

Professor Ramassamy stresses, however, that the dose of gemfibrosil used in mice would correspond to 400 or 600 milligrams in humans. This dose is already in use, but it comes with serious side effects, such as nausea and vomiting. There are also contraindications for patients with other health problems, including kidney or liver failure.

“When we know that people with Alzheimer’s disease often have several chronic diseases (…), there are still limitations,” he said.

Studies even suggest against using gemfibrosil in patients over 70 because of these complications, which could be problematic in fighting Alzheimer’s, Professor Ramassamy said.

At the very least, the work of the Chicago researchers could put scientists on new avenues that could lead to the identification of new compounds that are less toxic, but with the same effects.

For example, we already know that high cholesterol is a significant risk factor for Alzheimer’s disease, and several cholesterol drugs have been tested to combat it. The fact of fighting against cholesterol to improve or reduce cognitive deficit is therefore an interesting avenue, underlined Professor Ramassamy.

“Alzheimer’s disease is multifactorial, there are several mechanisms,” he said in conclusion. The fact of combining two compounds would perhaps make it possible to arrive at an interesting treatment. “

There are five times more astrocytes in the brain than there are neurons.

Around 55 million people are believed to have Alzheimer’s disease around the world. This figure could jump to 152 million by 2050 if no treatment is found.

The findings of this study were published by the scientific journal Science Signaling.


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