For nearly two decades, Ursula Quitterer, Professor of Molecular Pharmacology at ETH Zurich, pursued a single clue: brain tissue samples from Cairo that hinted at a protein at the heart of Alzheimer's disease. That persistence has yielded a breakthrough. Researchers at ETH Zurich have identified GRK2 as a key trigger of neurodegeneration and developed an experimental compound called Compound 10 that stops the disease cycle in its tracks—at least in mice.
The discovery matters because Alzheimer's remains one of medicine's most stubborn challenges. Current medications do not cure the disease; at best, they delay progression by a few months. The ETH Zurich team has found a completely different biological target, opening a new avenue for treatment that could eventually work alongside existing drugs to offer patients far greater benefit.
The story begins with those brain tissue samples, collected during tumor surgeries at Ain Shams University Hospital in Cairo from both people with dementia and those without. When Quitterer examined them, she found something striking: a protein called GRK2 existed in two forms. One worked normally. The other became inactive through cellular processes and, critically, accumulated in large amounts in the brains of people with dementia. The same pattern showed up in mice engineered to develop Alzheimer's-like symptoms.
Here is where the damage unfolds. The inactive GRK2 molecules clump together inside nerve cells and attach to mitochondria, the cellular powerhouses. "The GRK2 aggregates block the pores of the mitochondria, reducing the amount of energy they can supply and leading to a situation of stress inside the cells," Quitterer explains. Worse, the accumulating GRK2 also spurs production of amyloid beta, the protein fragment long associated with Alzheimer's. This creates a vicious cycle: amyloid beta stresses nerve cells, which triggers formation of more inactive GRK2, which accumulates further, accelerating the disease.
To break that cycle, the ETH Zurich team designed and tested several experimental compounds. Compound 10 emerged as the clear winner. In mice, it prevented GRK2 from clumping together, allowing mitochondria to work properly again. Nerve cells remained healthier, cell death slowed, and amyloid beta deposits shrank. The benefits extended beyond the brain—treated mice showed improved heart function and even developed fewer gray hairs as they aged, suggesting the compound's influence on aging-related changes more broadly.
Why did this research take so long? Alzheimer's, unlike cancer, is an age-related disease. The team worked with older mice, typically between one and a half and two years old, and each experiment required a similar span of time before meaningful conclusions emerged. "It's all a great deal slower than in cancer research," Quitterer notes.
The work has advanced to the patent stage, and ETH Zurich now seeks a company to shepherd Compound 10 toward human trials. Many hurdles remain—animal studies rarely translate directly to people—but the implications are real. For the first time, researchers have identified a new target protein and an active ingredient that operates through a completely different mechanism than existing Alzheimer's medications. That opens the possibility of combination therapies that could genuinely improve quality of life for millions facing this disease.