"FLAV-27 represents an innovative and promising approach to the treatment of Alzheimer's disease, with the potential to modify the course of the disease, as it not only targets its symptoms or a single pathological biomarker, but also directly targets the underlying molecular mechanisms," said Aina Bellver, a researcher at the University of Barcelona and the first author of the paper.
FLAV-27 is the first inhibitor of the G9a enzyme, a key regulator that normally "turns off" genes important for neuronal development, synaptic plasticity, and memory consolidation. In Alzheimer's disease, this process is disrupted. By blocking G9a, the drug restores normal neuronal function.
In experiments on various models, from cell cultures to mice, treatment with FLAV-27 not only reduced levels of classic disease markers (beta-amyloid and phosphorylated tau protein), but also led to functional recovery: improved short-term and long-term memory, spatial memory, and social behavior.
The researchers also identified blood biomarkers (H3K9me2, SMOC1, p-tau181) that correlate with disease severity and return to normal after treatment. This will allow future clinical trials to select patients using a simple blood test and monitor the effectiveness of therapy.
The findings confirm that epigenetic dysregulation is not simply a side effect, but a key mechanism linking the underlying pathological processes in Alzheimer's. Thus, the study opens the way to a new class of etiotropic drugs that modify the course of the disease, according to the press release.
The next stage is toxicology studies and preparation for human clinical trials. Commercialization will be handled by Flavii Therapeutics, a company founded in 2025 at the University of Barcelona that holds an exclusive license for FLAV-27.
More than a decade ago, scientists discovered a "skeletal" structure in neurons, which until then had been considered a passive support structure. A recent study showed that this structure is far from passive, but rather acts as a gatekeeper, helping prevent the aggregation of protein plaques in the brain.
