Saracatinib (AZD050) is a potential treatment for Alzheimer’s disease that is being studied by researchers at Yale University. The compound was originally developed as a cancer drug by AstraZeneca, but was discontinued because it did not seem effective. The company continues to provide the repurposed compound to Yale researchers as a potential Alzheimer’s therapy.

How saracatinib works

Saracatinib inhibits enzymes called protein kinases from the Src/Abl family.

During the study of saracatinib’s anti-cancer effects, it was found that the compound was effective in blocking the Fyn kinase.

The Fyn kinase is involved in mediating the toxicity of beta-amyloid, one of the major proteins thought to be responsible for brain cell damage observed in Alzheimer’s disease.

After saracatinib is administered, it targets and inhibits Fyn kinase, which causes the disruption of molecular pathways leading to the formation of insoluble beta-amyloid plagues.

Scientists believe that through this mechanism, saracatinib could prevent or delay the progression of Alzheimer’s disease.

One study investigated the role of saracatinib in reversing memory loss in mice. In this study, saracatinib was administered to mice with Alzheimer’s-like symptoms such as memory loss. The results, published in the scientific journal Annals of Neurology, revealed that saracatinib was effective in targeting Fyn kinase and successfully reversed memory deficits in mice.

Saracatinib in clinical trials

Promising results in animal studies led researchers to investigate the safety and tolerability of saracatinib in a Phase 1b multiple ascending oral dose study in humans (NCT01864655). The trial was completed and the results were published in the scientific journal Alzheimer’s Research & Therapy. They showed that saracatinib was safe and well-tolerated in patients with mild-to-moderate Alzheimer’s disease.

Based on these findings, researchers decided to investigate the safety and tolerability of saracatinib in a larger study. A Phase 2a multi-center trial (NCT02167256) was being conducted to evaluate the safety, tolerability, and effectiveness of saracatinib in treating patients with a mild form of Alzheimer’s disease. The study recruited 159 participants who were divided between treatment and placebo groups. The study completed in August of 2019 and the results of the study were published in the Journal of the American Medical Association: Neurology. The study followed patients for 52 weeks and observed if there were changes in the brain’s metabolism of glucose (sugar), cognitive and functional measures, and the size of brain areas through imaging techniques. None of the measures showed a statistical difference between the treatment and placebo groups but there was a trend towards less shrinkage in the hippocampus and entorhinal regions of the brain in the saracatinib group.

 

Last Updated: Aug. 26, 2019

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