Researchers have identified a previously unknown driver of Alzheimer’s disease and developed an experimental compound that blocks it, offering a potential new treatment strategy for the devastating condition. The compound, known as Compound 10, reduced nerve cell loss and extended survival in mice by targeting a protein called GRK2, which current Alzheimer’s drugs do not address.
The discovery stems from nearly two decades of work led by Ursula Quitterer, a professor of molecular pharmacology at ETH Zurich. Her team analyzed human brain tissue from people with and without dementia and found that an inactive form of the GRK2 protein accumulates in large amounts in Alzheimer’s patients. In nerve cells, these inactive GRK2 molecules clump together and attach to mitochondria, the energy-producing structures inside cells. “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 explained. This stress then triggers increased production of amyloid beta, the protein fragment long associated with Alzheimer’s, creating a damaging cycle that accelerates the disease.
To break this cycle, the team tested several experimental compounds in cell cultures and mice. Compound 10 emerged as the strongest candidate. It prevented GRK2 molecules from forming harmful aggregates, allowing mitochondria to function properly. In treated mice, amyloid beta deposits decreased, nerve cells remained healthier, and cell death slowed. The compound also appeared to improve heart function and even influenced aging-related changes, with treated animals developing fewer gray hairs as they grew older. The researchers have filed a patent application for Compound 10 and are now seeking a company to advance it toward drug development.
A New Target for a Complex Disease
Current Alzheimer’s medications do not cure the disease and at most delay its progression by several months. “That’s why it’s so important that we’ve now identified a new target protein in the form of GRK2, as well as an active ingredient that operates via GRK2 and therefore via a different mechanism than existing Alzheimer’s drugs,” Quitterer said. Because Alzheimer’s is an age-related condition, experiments with older mice took considerable time, with each study lasting one and a half to two years before meaningful conclusions could be drawn.
While much more research is needed before Compound 10 could be tested in humans, the discovery opens the door to a new treatment strategy. Researchers believe that combining Compound 10 with existing Alzheimer’s medications could eventually provide greater benefits and improve quality of life for patients. The team is optimistic that this new approach may one day offer hope to millions affected by the disease.