Scientists at ETH Zurich have developed an experimental compound that may offer a new way to slow some of the damage caused by Alzheimer’s disease.
The treatment, known for now as “Compound 10,” has produced encouraging results in mice, but it has not yet been tested as an Alzheimer’s treatment in people.
The research was led by Ursula Quitterer, Professor of Molecular Pharmacology at ETH Zurich. The findings were published in the journal Cell Reports Medicine.
Alzheimer’s disease is the most common cause of dementia. It gradually damages brain cells, leading to worsening problems with memory, thinking, communication, and the ability to manage everyday life.
Scientists know that Alzheimer’s is extremely complicated. Several harmful changes can occur in the brain, including the buildup of abnormal proteins, inflammation, problems with communication between nerve cells, and failure of the systems that provide cells with energy.
Quitterer’s research points to another possible part of this process. Her team focused on an enzyme called GRK2, which normally helps cells respond to signals and cope with stress.
The story behind the discovery began almost 20 years ago. Quitterer received brain tissue collected during tumor surgery from patients treated at Ain Shams University Hospital in Cairo, including samples from people with dementia and people without dementia.
When the researchers examined these samples, they found unusually high levels of an inactive form of GRK2 in tissue from people with dementia. Similar changes later appeared in mice used to study Alzheimer’s disease.
Normally, GRK2 has useful jobs in cells, including cells in the brain and heart. But the researchers found that when the enzyme becomes inactive, it can start sticking together and forming clumps inside brain cells.
These clumps appear to collect on mitochondria, tiny structures that produce much of the energy cells need. Healthy mitochondria are especially important in the brain because nerve cells require a large and steady supply of energy.
The researchers found that GRK2 clumps could interfere with pores in the mitochondria. This reduced their ability to provide energy and increased stress inside the cells, creating conditions that could make nerve cells more vulnerable to damage.
The team also found a possible connection with amyloid beta. This protein can build up in the brains of people with Alzheimer’s, and abnormal accumulations of it have long been a major focus of dementia research.
In the mouse experiments, inactive GRK2 appeared to encourage greater production of amyloid beta. The amyloid beta then placed more stress on cells, which could promote still more inactive GRK2 and more clumping.
This suggested a damaging cycle. Once the process begins, cell stress and abnormal proteins may reinforce each other and contribute to continuing loss of nerve cells.
Quitterer and her colleagues designed several chemicals in an attempt to interrupt this process. Compound 10 stood out because it prevented GRK2 from forming harmful clumps in laboratory experiments and in mice.
When the clumping was reduced, mitochondria worked better and less amyloid beta accumulated. The treated mice also showed less nerve-cell loss and lived longer than untreated animals in the experiments.
The researchers noticed effects outside the brain as well. Compound 10 appeared to support heart function and influence some age-related changes in mice, including the development of grey hair.
Those findings are interesting because GRK2 is active in many parts of the body. They raise the possibility that the processes being studied are connected not only with Alzheimer’s but also with broader changes that occur during aging.
However, the results remain at a very early stage. A treatment that works in cells or mice may fail in humans because people have far more complex biology, and researchers still need to determine the compound’s safety, suitable dose, and possible side effects.
The team has applied for patent protection and is looking for a company to help move the compound through further drug development. That process could require extensive testing before human clinical trials are possible.
The study is valuable because it identifies GRK2 as a possible new treatment target. Most current Alzheimer’s treatments do not cure the disease, and even newer drugs that target amyloid provide limited benefits for selected patients.
Compound 10 takes a different approach by targeting the abnormal behavior of GRK2 and the stress surrounding mitochondria. If future research confirms the findings, such a treatment might eventually be used alongside other Alzheimer’s medicines rather than replacing them.
The strongest part of the study is that the researchers connected observations in human brain tissue with detailed experiments in cells and animals. That gives the proposed mechanism more support than a finding based on a single type of experiment.
Still, the study does not show that Compound 10 slows Alzheimer’s disease in people. The longer survival and reduced nerve-cell damage seen in mice are promising signals, but they should be viewed as a starting point for drug development rather than evidence of a new human treatment.
Overall, the research opens an interesting new direction in Alzheimer’s science. Its real importance will depend on whether future studies can show that blocking GRK2 clumping is safe, reaches the human brain effectively, and produces meaningful improvements in patients.
Source: ETH Zurich.
