ETH Zurich Researchers Develop ‘Compound 10’ to Potentially Slow Alzheimer’s Progression

Ursula Quitterer, a Professor of Molecular Pharmacology at ETH Zurich, has led a research team in developing “Compound 10,” a chemical substance that may slow the progression of Alzheimer’s disease. Initial tests in mice have shown promising results, revealing a significant reduction in nerve cell death commonly associated with dementia and an increase in the lifespan of the treated animals.

Origins of Compound 10

The research on Compound 10 began nearly 20 years ago when Quitterer obtained brain tissue samples from patients at Ain Shams University Hospital in Cairo. These samples were taken from individuals with dementia and non-dementia patients during tumor surgeries. Quitterer utilized these samples to study an enzyme known as GRK2, which has been a key focus of her research.

GRK2 plays a vital regulatory role in human cells, helping them respond to various signals, stress, and strain. The enzyme’s activity is essential in several organs, including the brain and heart, and supports normal nerve cell functions. Recent analyses of the Cairo tissue samples, coupled with mouse experiments, revealed significant evidence of GRK2’s role in dementia, findings that have been published in Cell Reports Medicine.

Mechanism Behind GRK2 Dysfunction

GRK2 exists in two forms: a normal, functional form and an inactivated form, which develops through cellular metabolism. Quitterer’s research uncovered unusually high levels of the inactive form in the brain tissue of dementia patients and also in a mouse model for Alzheimer’s. Inactive GRK2 aggregates can accumulate within brain cells, obstructing mitochondrial function—critical cellular powerhouses—and contributing to stress within cells.

As explained by Quitterer, “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.” Additionally, the team found that inactive GRK2 appears to promote increased production of amyloid beta, a protein fragment implicated in Alzheimer’s pathology. This process can create a feedback loop that exacerbates neuronal stress and encourages further GRK2 inactivation and aggregation.

Compound 10’s Effects

To disrupt this damaging cycle, the research team created and tested multiple chemical compounds, with Compound 10 emerging as particularly effective. It successfully prevented the aggregation of GRK2, thereby enhancing mitochondrial function, reducing amyloid beta accumulation, and enabling nerve cells to maintain their health and functionality.

Moreover, the benefits of Compound 10 extend beyond the brain. The compound showed positive effects on heart function and aging processes in mice, with observed results such as older mice developing fewer grey hairs. However, these findings remain preclinical and Compound 10 is not yet available as a treatment for humans.

The Path Forward

The research team has recently applied for a patent for Compound 10 and completed the basic research phase. According to Quitterer, the lengthy timeline associated with Alzheimer’s research is due to the complexities of the disease and the necessity to conduct experiments using older animal models, approximately one and a half to two years old.

“It took so long simply because everything takes so long in Alzheimer’s research,” she explained, noting that each experiment typically requires about one and a half to two years for conclusive results and planning subsequent studies. The team is actively seeking collaboration with a company to advance Compound 10 into the next stages of drug development.

A New Therapeutic Strategy

Quitterer emphasizes the complexity of Alzheimer’s disease, noting that current treatments do not offer cures but can merely delay progression for several months. The identification of GRK2 as a target protein, along with the development of Compound 10, represents a potentially novel approach to treating Alzheimer’s. Because it operates through a different mechanism than existing drugs, there is hope that Compound 10 could complement conventional therapies and enhance the quality of life for Alzheimer’s patients.