After nearly two decades of work, researchers at ETH Zurich have uncovered a new mechanism behind Alzheimer's disease and developed a compound that breaks it.
The culprit they identified is GRK2, a cellular enzyme that, in the brain tissue of dementia patients, becomes inactivated and aggregates, clumping together in a way that damages mitochondria and feeds a self-reinforcing cycle of amyloid-beta production. Two hallmark Alzheimer's proteins, beta-amyloid and a tau variant, appear to set that harmful clumping in motion.
To break the loop, the team developed a targeted molecule they call Compound 10. It prevents GRK2 from aggregating, preserves the cell's energy output, and significantly delays nerve-cell death.
In mouse models, the results were encouraging on several fronts at once: the treatment reduced nerve-cell loss, lowered amyloid-beta levels, helped the animals live longer, and appeared to promote healthier aging overall.
What makes the finding notable is where it aims. For decades, Alzheimer's drug development has concentrated on clearing amyloid plaques and tau tangles, with billions spent for only modest benefit. Compound 10 targets a process those therapies leave untouched, which is why the team believes it could one day complement existing medications rather than replace them.
The caution is real: this is preclinical work in mice, and much more research is needed before any human testing. But it opens a treatment strategy that didn't exist before, built on post-mortem brain tissue collected during surgeries almost 20 years ago.
“"Targeting enzymes in drug development offers key advantages due to their well-defined active sites or 'pockets' where drugs can attach and block their activity."”Ursula Quitterer · Professor of Molecular Pharmacology · ETH Zurich