ST. LOUIS — A new drug capable of destroying brain-damaging proteins could soon lead to a treatment for neurodegenerative diseases like Alzheimer’s and Parkinson’s disease.
A team from the Washington University School of Medicine in St. Louis say the compound cleared harmful proteins from the brain in mice experiments. It offers hope of reversing age-related cognitive decline.
Researchers say the treatment rejuvenates immune cells surrounding grey and white brain matter. These cells sweep out waste but slow up in people and rodents with Alzheimer’s.
“Alzheimer’s has been studied for many years from the perspective of how neurons die, but there are other cells, such as immune cells on the periphery of the brain, that also may play a role in Alzheimer’s,” says senior author Jonathan Kipnis, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology & Immunology, in a university release.
“It doesn’t look likely that we will be able to revive dead or dying neurons, but the immune cells that sit on the borders of the brain are a feasible target for treating age-related brain diseases,” Kipnis adds. “They’re more accessible, and could be drugged or replaced. In this study, we treated aged mice with a molecule that can activate aged immune cells, and it worked in improving fluid flow and waste clearance from the brain. This holds promise as an approach to treating neurodegenerative diseases.”
What happens in the brain when someone has Alzheimer’s?
In patients with Alzheimer’s, rogue proteins known as amyloid beta and tau clump together, killing neurons. They trigger the hallmark symptoms of memory loss and confusion. The chemicals have also been linked to the onset of Parkinson’s disease, which also does not have a definitive cure currently. Finding a way to get rid of them is a potential gamechanger.
Prof. Kipnis and colleagues identified key immune cells called macrophages that cleanse the brain’s vessels.
“Cerebrospinal fluid flow is impaired in numerous neurodegenerative diseases, such as Alzheimer’s, stroke, Parkinson’s and multiple sclerosis,” says Antoine Drieu, PhD, a postdoctoral researcher and the paper’s lead author. “If we can restore fluid flow through the brain just by boosting these macrophages, maybe we can slow the progression of these diseases. It’s a dream, but who knows? It might work.”
Further analysis revealed that these macrophages change in Alzheimer’s patients. The immune cells are less able to consume and dispose of waste. Study authors found those most important are scarce in older mice. So, they administered a protein that boosted their activity.
The immune cells started behaving more like those from younger mice. Further, the treatment improved fluid flow and waste clearance from the rodents’ brains.
“Collectively, our results show that parenchymal border macrophages could potentially be targeted pharmacologically to alleviate brain clearance deficits associated with aging and Alzheimer’s disease,” says Kipnis, who is also a professor of neurology, neuroscience, and neurosurgery.
“I am discussing with colleagues how we can replace or rejuvenate those cells in aging brains and as a treatment for Alzheimer’s. I hope that one day we will be able to slow down or delay the development of age-related brain diseases with this approach.”
Cleaning out the brain helps Alzheimer’s drugs work better
Prof. Kipnis is an expert in the blossoming field of neuroimmunology, the study of how the immune system affects the brain. In 2015, he discovered a network of vessels that drains fluid, cells, and small molecules from the brain into the immune system’s lymph nodes.
Last year, his team showed some investigational Alzheimer’s therapies are more effective in mice when paired with a treatment geared toward improving drainage of fluid and debris from the brain.
Prof. Kipnis directs a program supported by a $15 million grant from the National Institutes of Health (NIH). It explores how macrophages and other immune cells interact with fluid flow and drainage in the brain during aging.
Projections show the number of dementia cases worldwide will soar to more than 150 million by 2050.
The study is published in the journal Nature.
South West News Service writer Mark Waghorn contributed to this report.
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