Researchers at ETH Zurich have identified an experimental compound that prevents a regulatory enzyme called GRK2 from forming harmful aggregates in brain cells. The study, published in Cell Reports Medicine, used brain tissue from dementia patients and a mouse model of Alzheimer's disease to trace how inactive GRK2 accumulates on mitochondria, blocking energy production and increasing amyloid beta levels.
The team, led by Professor Ursula Quitterer of Molecular Pharmacology, found that inactive GRK2 clumps were unusually abundant in both human dementia tissue and Alzheimer's-model mice. These aggregates settled on mitochondrial pores, reducing cellular energy supply and creating stress that further promoted amyloid beta production, which in turn encouraged more GRK2 inactivation — a self-reinforcing cycle.
After screening several chemical candidates, the researchers selected one designated Compound 10 for its ability to prevent GRK2 aggregation in cell cultures. In aged mice — roughly 1.5 to 2 years old — treatment with Compound 10 reduced amyloid beta accumulation, preserved mitochondrial function, slowed nerve cell death, and extended survival compared with untreated controls.
Unexpectedly, the compound also improved measures of heart function and reduced visible signs of aging such as graying fur in the treated mice. Quitterer noted that these broader effects suggest GRK2 aggregation may influence aging processes beyond Alzheimer's pathology, though the findings remain preclinical.
The research began nearly 20 years ago with brain tissue samples from Ain Shams University Hospital in Cairo. Because Alzheimer's is age-related, experiments required older mice, making each study cycle last 1.5 to 2 years. Quitterer said this timeline is substantially slower than research in fields such as oncology.
ETH Zurich has filed a patent on Compound 10 and is seeking a commercial partner to advance the compound toward clinical development. The researchers emphasize that existing Alzheimer's drugs only modestly delay progression, and because Compound 10 acts through a different mechanism — targeting GRK2 aggregation rather than amyloid directly — it could potentially complement current therapies if it proves safe and effective in humans.
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