Ursula Quitterer and her research team have developed an experimental compound that may slow the progression of Alzheimer’s disease. Known as “Compound 10,” the potential treatment has shown promising results in studies involving mice.
Quitterer, a professor of molecular pharmacology at ETH Zurich, has been testing experimental Alzheimer’s treatments in animal models. In the latest studies, Compound 10 significantly reduced the nerve cell death associated with dementia and helped treated mice live longer.
The research began nearly 20 years ago, when doctors and researchers at Cairo’s Ain Shams University Hospital provided brain tissue samples collected during tumor surgery. The samples came from patients with dementia and from patients without dementia, allowing scientists to compare the biological differences between the two groups.
New drug target for Alzheimer’s disease
Quitterer used the tissue samples to study an enzyme called GRK2, which has been a central focus of her research for many years.
GRK2 performs important regulatory functions in human cells. It helps cells respond appropriately to signals, stress, and changes in their environment. The enzyme is active in organs including the heart and brain, where it contributes to normal nerve cell function.
By analyzing the Cairo tissue samples at the molecular level and conducting experiments in mice, Quitterer and her colleagues found evidence that GRK2 plays an important role in Alzheimer’s disease and dementia. Their findings were recently published in the journal Cell Reports Medicine.
What happens when GRK2 stops working?
GRK2 occurs in cells in two forms. One form is normal and functional, while the other becomes inactive through the cell’s metabolic processes.
Quitterer’s team found unusually high levels of inactive GRK2 in the brain tissue of patients with dementia. The researchers observed the same pattern in a mouse model of Alzheimer’s disease.
They also discovered that inactive GRK2 can form aggregates inside brain cells as dementia progresses. These aggregates may accumulate in mitochondria—the “powerhouses” of cells—interfering with their normal function and causing cellular damage.
“GRK2 aggregates block the mitochondrial pores, reducing the amount of energy they can provide and creating a stress situation within the cell,” explains Professor Quitterer.
Experiments in mice revealed another important effect: inactive GRK2 appears to increase the production of amyloid beta, a protein fragment strongly associated with Alzheimer’s disease.
This process may create a damaging feedback loop. Amyloid beta places additional stress on neurons, while that stress promotes the formation of more inactive GRK2 and additional GRK2 aggregates. Over time, this vicious cycle may contribute to the progression of dementia.
Compound 10 interrupts the harmful cycle
To disrupt this process, Quitterer and her colleagues developed several experimental compounds and tested them in cell cultures and mice.
Compound 10 produced the most promising results. The compound prevented GRK2 molecules from forming harmful aggregates and improved mitochondrial function. Researchers also observed lower levels of amyloid beta inside cells, helping nerve cells maintain their function and avoid premature death.
The effects of Compound 10 were not limited to the brain.
In mice, the compound also improved heart function and appeared to influence certain aspects of the aging process. One visible example was reduced gray hair in older animals.
Unexpected effects on aging
The broad effects of Compound 10 suggest that targeting GRK2 aggregation may influence biological processes beyond those directly linked to Alzheimer’s disease.
Along with protecting nerve cells and supporting mitochondrial health, the compound appeared to benefit heart function and reduce some signs of aging in mice.
However, the research remains at the preclinical stage. Compound 10 has not yet been developed or approved as a treatment for humans.
Why does Alzheimer’s disease research take years?
The researchers have applied for a patent covering Compound 10 and have completed the initial laboratory research stage.
“The reason it took so long is because everything in Alzheimer’s disease research is so time-consuming,” Quitterer explains.
Because Alzheimer’s disease is associated with aging, the research team needed to conduct experiments on older animals. In mice, this generally means studying animals between approximately 1.5 and 2 years old.
In addition, individual experiments can take around one and a half to two years before researchers have enough data to draw conclusions and plan the next stage of research.
“It takes much longer than, say, cancer research.”
Quitterer and ETH Zurich are now seeking pharmaceutical and biotechnology companies interested in advancing Compound 10 through the next stages of drug development.
A different approach to Alzheimer’s disease treatment
“Alzheimer’s disease is a very complex disease,” Quitterer said.
Existing Alzheimer’s drugs cannot cure the disease. At best, some treatments can slow its progression for a limited period of time.
“That is why it is so important that we have identified a new target protein in the form of GRK2 and an active ingredient that acts through GRK2 and therefore by a different mechanism than existing Alzheimer’s drugs.”
Because Compound 10 targets a different biological pathway, researchers believe it could potentially complement existing Alzheimer’s treatments rather than replace them.
If future studies confirm its safety and effectiveness, Compound 10 could one day be used alongside other medications to help improve the quality of life of people living with Alzheimer’s disease.
Source: www.sciencedaily.com