When the nerve cells in the brain die, Alzheimer’s disease occurs. The mechanism that leads to the death of brain cells was not yet known. However, an explanation would help find therapies to stop dementia. Now Belgian researchers led by Bart de Strooper show in the scientific journal ‘Science’ how the mechanism that causes brain cells to die works.
According to their research, the molecule MEG3 is responsible. To find out, researchers from the University of Leuven worked with Alzheimer’s mice, which, like Alzheimer’s patients, produce large clumps of protein in their brains. Precursors of human nerve cells were implanted into the mice, which developed into nerve cells within a few weeks.
After a few months the test animals became ill. Fibrous protein clumps accumulated in the cells between the protein clumps, and later many of the affected nerve cells died. The same thing happened in the brains of Alzheimer’s mice as in people with dementia. In addition, the clumps and glued fibers significantly disrupted the processes in the nerve cells. The research subsequently showed that there was ten times more of the MEG3 molecule in these cells than in healthy brains.
The Belgian research team is now convinced that the abundance of MEG3 caused cell death. This is because the nerve cells implanted in the mice survived when the molecule was switched off in the test animals. A second experiment confirmed the theory: the nerve cells died in a culture dish when MEG3 was added. Without MEG3 they survived. Moreover, this molecule is also present in large quantities in Alzheimer’s patients, write the researchers led by de Stooper.
The study could therefore solve the great mystery of dementia. Does the MEG3 molecule therefore pave the way for new therapies? “The extent of MEG3’s influence is still completely unclear,” says Ansgar Felbecker, chairman of the Swiss Memory Clinics. In particular, the issue of causality has not yet been clarified by this study. “MEG3 was upregulated in Alzheimer’s patients, but whether this is the beginning of the entire disease cascade or a secondary effect as part of the disease has not yet been clarified in the current study,” says the neurologist from the Cantonal Hospital of St. Gallen. .
According to Felbecker, it is therefore not possible to say what percentage of MEG3 is responsible for Alzheimer’s disease. Furthermore, the exact mechanism is not yet known in humans, despite evidence in mice. “We cannot simply draw conclusions about effects in the human brain from laboratory research. This has repeatedly led to false conclusions in the past, and I would be very careful about making any statement here,” Felbecker said.
But for De Stooper and other scientists it is clear that the research results are clear enough to use them in the development of a new Alzheimer’s drug. One that stops the molecule, a MEG3 blocker. Apparently, substances already exist that counteract the action of MEG3 in cells. Such a drug has already been approved in the US to treat tumors.
There is still no truly effective Alzheimer’s drug. The latest Alzheimer’s therapy Lecanemab from the companies Biogen and Eisai was declared a new hope this year and received approval from the US Food and Drug Administration (FDA) in the spring.
Like most therapies, lecanemab targets the protein amyloid; other, even less developed therapies target the protein tau. The study results showed that lecanemab reduced amyloid deposits and slowed cognitive decline at a very early stage of the disease. However, the progression of dementia was only minimally slowed. A drug that stops cell death in a different way would therefore be very welcome.
According to the Belgian researcher, a MAG3 blocker would create a new type of medicine. It is not yet possible to say whether the previously unsuccessful focus on amyloid and tau will be eliminated, Felbecker explains. “In principle, Alzheimer’s research is already intensively looking for approaches that go beyond amyloid and tau – but that does not mean that these two recognized pathologies would no longer be used; that would certainly be wrong.”
What MEG3 therapy might one day look like cannot be answered at this time. “The fact is that in the past it often took up to twenty years before such fundamental research results were converted into therapies,” says the head of the Alzheimer’s clinic. Lecanemab is a current example of this. Basic research into this started twenty years ago.
Since the corona pandemic, we know that things can happen faster. But still: research into dementia is complex and takes time, says the chairman of the Swiss Memory Clinics, Ansgar Felbecker. “And unfortunately, 99 percent of potential therapeutic approaches fail along this path – whether it is because side effects occur, there is no effect in humans or because no one is willing to invest the large sums of money needed for clinical trials.”
(aargauerzeitung.ch)
source: watson
I’m Maxine Reitz, a journalist and news writer at 24 Instant News. I specialize in health-related topics and have written hundreds of articles on the subject. My work has been featured in leading publications such as The New York Times, The Guardian, and Healthline. As an experienced professional in the industry, I have consistently demonstrated an ability to develop compelling stories that engage readers.
