The Enzyme Trapped in a Vicious Circle: How ETH Zurich’s “Compound 10” Could Slow Alzheimer’s

Alzheimer’s research moves at a punishing pace. Because the disease is age-related, scientists have to work with old mice, and each experiment can take a year and a half to two years before it even yields conclusions worth building on. “It’s all a great deal slower than in cancer research,” says Ursula Quitterer, Professor of Molecular Pharmacology at ETH Zurich. Her team has spent almost twenty years chasing a single culprit and they may have finally found a way to disarm it.

An enzyme with a split personality

The story starts with GRK2, an enzyme found throughout the body that normally helps cells respond to stress and signalling. In the brain, it supports the day-to-day function of nerve cells. But GRK2 comes in two forms: a healthy, active one, and a version that cellular metabolism has switched off.

Working with brain tissue samples collected from patients in Cairo, some with dementia, some without, and with a mouse model of Alzheimer’s, Quitterer’s team found that the inactive form of GRK2 piles up in dementia brains. Worse, it doesn’t stay harmlessly out of the way. It clumps together into aggregates that latch onto mitochondria, the cell’s energy factories, and physically block their pores. Energy production drops, and the cell is thrown into a state of chronic stress.

A feedback loop that feeds itself

Here’s where it gets nasty. The stressed mitochondria push nerve cells to produce more amyloid beta, the sticky protein fragment long implicated as a driver of Alzheimer’s. Amyloid beta then stresses the cells further, and that stress generates still more inactive, aggregating GRK2. Cause becomes effect becomes cause again, a self-perpetuating cycle that keeps the disease advancing.

Breaking a loop like that means finding the right point to intervene. The team synthesized a series of candidate compounds and tested them in cell cultures and in mice. One of them, referred to simply as “compound 10,” stood out: it stopped GRK2 molecules from aggregating in the first place. With the aggregates cleared out of the way, mitochondria worked properly again, amyloid beta deposits dropped, and nerve cells stopped dying off at their usual accelerated rate. Treated mice survived longer than untreated ones.

An unexpected bonus

Compound 10’s effects weren’t confined to the brain. Treated mice also showed better heart function and slower signs of ageing overall, including, notably, fewer grey hairs in old age. It’s a reminder that GRK2 dysfunction and mitochondrial stress aren’t purely a neurological story; they touch aging biology more broadly.

Why this matters

Current Alzheimer’s medications don’t cure the disease, at best, they delay its progression by a few months. What makes compound 10 interesting isn’t just that it worked in mice, but that it works through a completely different mechanism than existing drugs, by targeting GRK2 rather than amyloid beta directly. That opens the door to combination therapies down the line. Quitterer’s team has filed a patent on the compound and is now looking for a pharmaceutical partner willing to carry it through the long process of drug development. Given how slowly this field moves, that next stage could itself take years, but the basic science, two decades in the making, is done.

Original paper: Abd Alla J, Perhal A, Fu X, Langer A, el Faramawy Y, Quitterer U. Analysis of GRK2 aggregation in the pathology of Alzheimer disease in animal models. Cell Reports Medicine, 2026. 

Source: The Enzyme Trapped in a Vicious Circle: How ETH Zurich’s “Compound 10” Could Slow Alzheimer’s