New Compound Offers Hope for Alzheimer’s Treatment

A team of researchers has come up with an innovative compound that might change how we approach the treatment of Alzheimer’s disease. This could be more than just another treatment; it might pave the way for a new strategy in managing the most prevalent form of dementia globally.

Most existing Alzheimer’s medications focus on eliminating amyloid-beta plaques, which are closely linked to the disease. In contrast, this new compound specifically targets an enzyme, aiming to reprogram the epigenome of neurons. This refers to the molecular tags that can be added to or taken away from DNA, effectively altering gene function.

Current monoclonal antibody therapies, like lecanemab and donanemab, have shown limited success in slowing down disease progression if initiated early, but no definitive method exists to reverse cognitive decline in Alzheimer’s patients. Treatments focusing on a protein called tau haven’t yielded effective results either.

This situation has prompted researchers to rethink our understanding of Alzheimer’s disease. Perhaps we’ve been concentrating too much on proteins that signify the illness, rather than addressing its underlying causes.

The newly developed compound, known as FLAV-27, takes a broader perspective, focusing on upstream changes in gene expression that contribute to the disease’s progression, beyond just the issue of protein plaques.

Aina Bellver-Sanchis, a molecular biologist at the University of Barcelona Institute of Neurosciences, remarked that FLAV-27 represents a promising new direction in treating Alzheimer’s. She suggests that it could influence the disease’s pathway, engaging with its molecular mechanisms rather than merely alleviating symptoms or targeting a single biomarker.

While the advent of monoclonal antibodies signifies progress in Alzheimer’s treatment, Bellver-Sanchis and her team point out that drugs like lecanemab and donanemab only manage to slow cognitive decline by about 30% and do not encompass the full breadth of the disease.

FLAV-27 uniquely inhibits an enzyme known as euchromatic histone-lysine N-methyltransferase 2 (EHMT2), or G9a. This enzyme plays a key role in regulating gene expression in the brain, silencing essential genes for processes like brain cell development and memory.

The compound works by blocking a molecule called S-adenosylmethionine, which essentially removes the enzyme’s influence on genetic expression. Early findings indicate that inhibiting G9a may help restore a more typical function to brain cells facing epigenetic dysregulation associated with Alzheimer’s.

While FLAV-27 has shown promising results in cell studies and tests on nematodes and mice, it has yet to undergo human trials. It demonstrated the ability to reduce amyloid-beta plaques, as well as improve some damage caused by Alzheimer’s in animal models.

Notably, in studies with nematode worms, FLAV-27 enhanced mobility, prolonged lifespan, and increased mitochondrial respiration, which is vital for cell energy. In mouse models, both early- and late-onset Alzheimer’s showed improvements in memory, social interactions, and the functionality of synapses connecting brain cells.

These findings suggest that epigenetic dysregulation could play a central role in linking various Alzheimer’s markers, rather than merely being a byproduct of the disease.

Although FLAV-27 appears promising, like other drug candidates, it still has a lengthy path ahead before reaching human trials, requiring toxicology studies in at least two animal species and compliance with regulatory requirements.

The study detailing these findings was published in Molecular Therapy.