New Alzheimer's Drug Target Identified, Experimental Compound Shows Promise

Researchers at ETH Zurich have identified a new target for Alzheimer's disease treatment. They developed an experimental compound that blocks a damaging process within brain cells. In studies with mice, the treatment reduced nerve cell loss and extended lifespan. The compound also addressed a biological process not targeted by current Alzheimer's drugs.

The research, led by Professor Ursula Quitterer, focused on the protein GRK2. This protein helps cells respond to signals and adapt to stress. It supports healthy nerve cell function in the heart and brain. The team found that an inactive form of GRK2 accumulates in the brains of individuals with dementia and in mouse models of Alzheimer's disease.

Inactive GRK2 molecules form clusters inside nerve cells. These clusters attach to mitochondria, the cell's powerhouses, and disrupt their function. This interference reduces the energy supply to cells, causing stress. The researchers also observed that inactive GRK2 increases the production of amyloid beta, a protein associated with Alzheimer's disease. This creates a cycle where cellular stress leads to more inactive GRK2 and increased amyloid beta.

The experimental compound, named Compound 10, was designed to interrupt this cycle. It prevented GRK2 molecules from forming harmful aggregates. This allowed mitochondria to function more effectively. Compound 10 reduced amyloid beta deposits and slowed nerve cell death in mice. The treated animals also showed improved heart function and fewer gray hairs, suggesting broader anti-aging effects.

The research took nearly two decades due to the complex nature of Alzheimer's studies. The team worked with older mice, requiring extended observation periods for each experiment. ETH Zurich has filed a patent application for Compound 10. They are seeking a company to advance the compound toward drug development.

Researchers believe that targeting GRK2 offers a new mechanism for Alzheimer's treatment. Combining Compound 10 with existing medications could potentially improve patient outcomes. Further research is needed before the compound can be tested in humans.