Alzheimer's: Epigenetic compound FLAV-27 reverses cognitive decline in mice

Researchers report that FLAV-27, which inhibits the enzyme G9a (EHMT2), restored memory and social behaviour in mouse models and produced benefits in nematode and cell studies; the compound has not been tested in humans.

Researchers describe a new compound called FLAV-27 that therapeutically reprograms the neuronal epigenome by inhibiting the enzyme EHMT2 (G9a). The compound reduced pathological markers and restored memory and social behaviour in mouse models of Alzheimer’s disease. It also improved mobility, lifespan, and mitochondrial respiration in Alzheimer's-model nematode worms and showed effects in cell studies. The work was published in the journal Molecular Therapy. Key findings: - FLAV-27 is described as the first inhibitor to target EHMT2 (G9a) and acts by blocking S-adenosylmethionine, reducing the enzyme's influence on gene expression. - In lab-grown mouse brain cells and other cell studies, the compound reduced amyloid-beta plaques and tau tangles, which are commonly associated with Alzheimer's pathology. - In Caenorhabditis elegans models, FLAV-27 improved mobility, extended lifespan, and increased mitochondrial respiration. - In mouse models of both early- and late-onset Alzheimer's, the compound restored memory performance, social behaviour, and synapse function. - The compound remains preclinical; it has not been tested in humans and the researchers note the need for toxicology studies in at least two animal species and other regulatory steps before human trials. Summary: The study presents an epigenetic strategy that targets upstream gene-expression changes and produced functional improvements across cell, worm, and mouse models. Whether these results will translate to people is undetermined at this time. Further preclinical testing and regulatory review are required before any human studies can begin.