Experimental therapy offers new path in Alzheimer’s treatment

A new experimental Alzheimer’s therapy is offering researchers a markedly different way of approaching treatment. Rather than focusing solely on removing protein plaques, the compound appears to act on deeper regulatory processes that influence how neurons function and deteriorate over time.

Scientists at the University of Barcelona have developed a drug candidate that targets a fundamentally different mechanism from current approved therapies. Instead of primarily clearing beta-amyloid plaques from the brain, the compound—known as FLAV-27—aims to reset part of the cell’s epigenetic machinery, the system that controls which genes are switched on or off, as described in a SciTechDaily article.

In animal models, this approach appears to influence several core features of Alzheimer’s disease simultaneously, pointing to a broader therapeutic strategy compared with treatments that focus mainly on amyloid removal.

The findings, published in Molecular Therapy, highlight a potential new direction for treatment based on epigenetic regulation.

Alzheimer’s disease is typically associated with a combination of factors, including beta-amyloid buildup, tau pathology, inflammation, and the breakdown of synaptic communication. By targeting gene regulation rather than a single protein, researchers believe FLAV-27 may act closer to the root biological mechanisms of the disease.

“The compound FLAV-27 represents an innovative and promising approach to Alzheimer’s disease, with the potential to modify the disease process, as it acts not only on its symptoms or a single pathological biomarker, but directly on its underlying molecular mechanisms,” said Aina Bellver, a researcher at the UB Institute of Neurosciences and the study’s lead author.

Current treatments such as lecanemab and donanemab are monoclonal antibodies designed to clear beta-amyloid plaques from the brain. “Although they represent a breakthrough, their efficacy is limited, as they only slow cognitive decline by 27% to 35%, have several side effects and only address the part of the pathology caused by beta-amyloid accumulation,” the researchers explain.

FLAV-27 takes a different path. It is the first inhibitor of its kind to target the G9a enzyme, a key regulator in the brain’s epigenetic system that helps silence genes involved in neuronal development, synaptic plasticity, and memory formation.

The drug works by blocking the molecule S-adenosylmethionine (SAM) from binding to G9a—an interaction required for the enzyme to modify DNA. By disrupting this process, FLAV-27 appears to slow the epigenetic dysfunction linked to Alzheimer’s disease and may help neurons regain more normal activity.

By Nazrin Sadigova