Drug candidates CMS121 and J147 may improve memory deficits associated with Alzheimer’s disease

As part of a recent study by researchers at Salk Institute, drug candidates CMS121 and J147 were determined to improve memory and reduce the degeneration of brain cells among rodents with Alzheimer’s disease.

The study, published in eLife, focused on the two experimental treatments, CMS121 and J147, utilized in the past among rodents. Although how it reaches its beneficiary effects on cognition is not widely understood, researchers turned to molecular pathways and aging, both factors that contribute to Alzheimer’s, to get a better understanding of these potential treatments.

In the study, researchers experimented on rodents known to age fast, administering either CMS121 or J147 at nine months old, or roughly mid-adulthood in humans. Memory and behavior of the rodents were tested after four months, having analyzed genetic and molecular markers in the brain.

The results established, among the rodents, that the drug candidates induced beneficiary effects on memory, compared to their counterpart who did not receive either drug candidates. Additionally, researchers noticed distinct alterations at the cellular and molecular levels in the brain.

Furthermore, mitochondria was affected by both drug candidates, boosting the levels of acetyl-coenzyme A. “Both compounds preserved mitochondrial homeostasis by regulating acetyl-coenzyme A (acetyl-CoA) metabolism,” said Antonio Currais, co-author of the study.

“CMS121 and J147 increased the levels of acetyl-CoA in cell culture and mice via the inhibition of acetyl-CoA carboxylase 1 (ACC1), resulting in neuroprotection and increased acetylation of histone H3K9 in SAMP8 mice, a site linked to memory enhancement.”

“These data show that targeting specific metabolic aspects of the aging brain could result in treatments for dementia,” Currais determined.

Pamela Maher, co-author of the study, concluded: “This study further validated these two compounds not only as Alzheimer’s drug candidates but also as potentially more widely useful for their anti-aging effects.”

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