Blarcamesine Slows Progression of Alzheimer's Disease in a Human Trial

Is maladaptive loss of autophagy a meaningful contributing factor in Alzheimer's disease? The results of a recent clinical trial suggest so. Autophagy is the name given to a collection of cellular maintenance processes responsible for recycling unwanted proteins, molecular waste, and damaged cell components. Improving autophagy should in turn improve cell function. The drug development program noted here has reached the stage of later human trials to assess efficacy, and is focused on correcting one specific mechanism that appears to negatively affect autophagy in the Alzheimer's brain, and that in turn helps to clear out damaging protein aggregates associated with Alzheimer's disease pathology.

Blarcamesine works by selectively binding to the sigma-1 receptor (SIGMAR1), which is expressed at consistently high - if not increasing - levels in the brain of healthy aging adults. In Alzheimer's disease, however, SIGMAR1 expression drops. SIGMAR1 activation has also recently been linked with autophagy, the cellular process by which damaged organelles and faulty proteins are cleared. Treatment with blarcamesine leads to the upregulation of SIGMAR1 in the brain, which could potentially activate autophagy in the brain and help in the clearance of amyloid and tau deposits.

At 48 weeks of treatment, the change in the Alzheimer's Disease Assessment Scale-Cognitive Subscale version 13 (ADAS-Cog13) scores in blarcamesine-treated patients was significantly better than placebo comparators. Blarcamesine was likewise significantly better than placebo when cognition was evaluated using the Clinical Dementia Rating scale Sum of Boxes (CDR-SB) scale. Biomarker data showed that blarcamesine treatment resulted in a significant drop in pathological amyloid beta levels and a corresponding improvement in Aβ42/40 ratio, pointing to the molecule's strong anti-amyloid potential. The drug candidate also resulted in lower brain volume loss versus placebo.



Seems potentially like a big deal!

Is this related to the work from the Spanish researcher who name i cannot remember now and she works at Einstein college.

Posted by: Matt at September 25th, 2023 5:41 AM

That is a unique looking molecule. Their stock went up a a lot after the announcement in 2021, but has since fallen back quite a bit, just my five minute analysis.

Posted by: JohnD at September 25th, 2023 8:19 AM
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