Schizophrenia Drug Reduces Tau Protein Aggregation in Cell and Mouse Models, Study Finds

Graphic: schizophrenia drug reduces tau aggregation in cell and mouse models, study finds

Amisulpride, an antipsychotic drug, is capable of reducing aggregation of the tau protein in cell and mouse models, according to a study published earlier this year. While the drug could be a potential disease-modifying treatment for tau-based FTD, further trials with human participants are necessary.

Tau is one of a few proteins that can accumulate abnormally in the brains of people with FTD, which can negatively impact brain functioning. While conducting previous research, however, the study’s authors discovered that activation of serotonin receptor 7 (5-HT7R) plays a crucial role in tau accumulation. Using the compound SB-269970, the researchers were able to inhibit 5-HT7R and prevent the collection of tau.

As SB-269970 is a research compound not permitted for human use, the researchers conducted a separate study to evaluate how well several FDA-approved drugs could prevent tau accumulation.

The antipsychotic drugs amisulpride, clozapine, and lurasidone and the antidepressants mianserin and vortioxetine were selected for the study based on their structural similarity to SB-269970. Researchers used three different cell-based models and two mouse-based models to test the drugs.

Based on the results of the tests, amisulpride, mianserin, clozapine, and lurasidone all reduced tau’s ability to aggregate. Vortioxetine only had some of the desired effects and did not seem to sufficiently block 5-HT7R activity in a way that would reduce tau.

Amisulpride, commonly prescribed to treat schizophrenia, was the most effective at repressing 5-HT7R activity. An essential discovery of the study was that chronic oral administration of amisulpride to mice helped to alleviate the progression of tau-based FTD.

While the drug shows promise in a laboratory setting, the authors note that clinical trials with human participants are still necessary to evaluate the safety and efficacy of amisulpride and other 5-HT7R-targeting drugs as a disease-modifying treatment for FTD.

Co-senior author Dr. Evgeni Ponimaskin said that his team is preparing a phase 2 clinical trial to evaluate the efficacy of amisulpride as a dementia treatment.

Interested in learning more about FTD drug research? Click here to read a study about a drug study that identified compounds that could be used to treat ALS and proteins that could serve as drug targets.

Are you interested in learning what drug-based research is capable of? Click here to read about lecanemab, a drug recently approved by the FDA to treat Alzheimer’s disease.

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