A promising experimental compound developed by researchers at ETH Zurich could offer a new way to slow the progression of Alzheimer’s disease. In studies involving mice, the treatment reduced nerve cell loss, helped the animals live longer, and targeted a biological process that existing Alzheimer’s drugs do not address.
The compound, known by researchers as “Compound 10,” is the result of nearly two decades of work led by Ursula Quitterer, Professor of Molecular Pharmacology at ETH Zurich.
A Long Search for New Alzheimer’s Clues
The research began almost 20 years ago when Quitterer received brain tissue samples from a colleague at Ain Shams University Hospital in Cairo. The samples were collected during tumor surgeries and came from both people with dementia and individuals without the condition.
Those samples helped launch an investigation into a protein called GRK2, which has been the focus of Quitterer’s research for many years.
GRK2 plays an important role throughout the body. As a regulatory protein, it helps cells respond to signals and adapt to stress. It is active in several organs, including the heart and the brain, where it supports healthy nerve cell function.
Using both human brain tissue and mouse models of Alzheimer’s disease, the ETH Zurich team uncovered evidence that GRK2 may be a major contributor to dementia. Their findings were recently published in the journal Cell Reports Medicine.
When a Protective Protein Turns Harmful
GRK2 exists in two forms inside cells. One form functions normally, while the other becomes inactive through cellular processes.
The researchers found that the inactive version accumulates in large amounts in the brains of people with dementia. Similar patterns were also observed in mice that develop Alzheimer’s-like symptoms.
Further experiments revealed that inactive GRK2 molecules clump together inside nerve cells. These clusters attach to mitochondria, the structures often referred to as the “powerhouses” of cells, and interfere with their function.
“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.
The team also found that inactive GRK2 appears to increase the production of amyloid beta, a protein fragment widely associated with Alzheimer’s disease.
This creates a damaging cycle. Amyloid beta places additional stress on nerve cells, which leads to the formation of even more inactive GRK2. As more GRK2 accumulates and forms aggregates, the disease process continues to accelerate.
Compound 10 Breaks the Cycle
To interrupt this cycle, the researchers designed and tested several experimental compounds in cell cultures and mice.
Among them, Compound 10 delivered the strongest results. The compound prevented GRK2 molecules from forming harmful aggregates, allowing mitochondria to function more effectively. As a result, amyloid beta deposits were reduced, nerve cells remained healthier, and cell death was slowed.
The benefits extended beyond the brain.
In mice, Compound 10 also appeared to improve heart function and influence aging-related changes. The researchers observed that treated animals developed fewer gray hairs as they grew older.
Why the Research Took Nearly Two Decades
The team has completed the basic research phase and filed a patent application for Compound 10.
According to Quitterer, one reason the work took so long is the nature of Alzheimer’s research itself.
“It took so long simply because everything takes so long in Alzheimer’s research,” explains Quitterer.
Because Alzheimer’s is an age-related disease, the researchers worked with older mice. These animals were typically between one and a half and two years old. Each experiment required a similar amount of time before meaningful conclusions could be drawn and the next stage of research could begin.
“It’s all a great deal slower than in cancer research, for example.”
A New Target for Future Alzheimer’s Treatments
ETH Zurich and the researchers are now seeking a company interested in advancing Compound 10 toward drug development.
“Alzheimer’s is a very complex disease,” says Quitterer. Current medications do not cure the disease, but rather — 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.”
While much more research is needed before the compound could be tested in people, 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.
source: https://www.sciencedaily.com/
