UVA: Discovery Reveals Way to Stop Inflammation in Alzheimer's Disease, More

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University of Virginia researchers studying Alzheimer's University of Virginia researchers studying Alzheimer's
Researchers are trying to work around the blood-brain barrier Researchers are trying to work around the blood-brain barrier

It's not a cure yet, but University of Virginia researchers may be one step closer to identifying a way to treat Alzheimer's disease.

“We are actually working on mouse models to see if we can actually prevent the disease, or try and roll back or reverse the symptoms,” says Dr. Bimal Desai, an assistant professor in the department of pharmacology.

Evidence shows inflammation in the immune system plays a huge part - something the Alzheimer's Association has been looking at for years.

“We don't know the specific reason that Alzheimer’s develops yet,” says Sue Friedman, president and CEO of the Alzheimer’s Association. “So, it's important that we continue to look across several research fronts to make sure that we, in the end, do find the reason or the multiple reasons that Alzheimer’s is developing in the brain."

Typically, something known as the blood-brain barrier helps protect the brain. However, that barrier also prevents biological drugs from getting in to target the electrical switch in the brain that produces inflammation.

New findings that involve important immune cells may offer a way around that.

“By creating drugs against the switch, if we can actually prevent the switch from getting turned on during inflammation - we might be able to alleviate symptoms of Alzheimer's and also sepsis,” says Desai.

This can also help those battling conditions like sepsis, arthritis, and Parkinson's. It’s just one piece of a complex puzzle that will take at least another decade to solve.

The Alzheimer's Association has recently given a grant to doctors at the University of Virginia to look deeper into the potential correlation between brain injuries and Alzheimer's disease.

University of Virginia School of Medicine Press Release:

CHARLOTTESVILLE, Va., Feb. 26, 2018 – A new discovery about the immune system may allow doctors to treat harmful inflammation that damages the brain in neurodegenerative diseases such as Alzheimer’s. It might also let doctors save patients from the potentially deadly inflammation of sepsis, a full-body infection that kills a quarter-million Americans every year.

The finding “opens up a whole new research area to look at neuroinflammation in the context of Alzheimer’s and Parkinson’s,” said lead researcher Bimal Desai, PhD, of the University of Virginia School of Medicine. “But the clinical impact will be in many, many different areas.”

Neurological Treatments

Traditional treatments for neurological inflammation, such as in Alzheimer’s and Parkinson’s disease, are largely ineffective because biological drugs are blocked by what is known as the blood-brain barrier. That barrier protects the brain from dangers such as bacteria or toxins in the blood, but it also makes it very difficult to get drugs into the brain. “A lot of the drugs we use right now to treat inflammation, [known as] biologicals, don’t work in the brain because they can’t get through,” explained Desai, of UVA’s Department of Pharmacology and UVA’s Carter Immunology Center.

His new finding, involving important immune cells known as macrophages (and microglia), could offer a way around that. He and his team have identified a specific electrical switch, known as an ion channel, within macrophages that controls the flow of calcium into the cells. Without calcium, the cells can’t cause inflammation. By targeting this switch with tiny molecules, researchers could deny the macrophages calcium and prevent inflammation – even in the brain.

A Better Way to Battle Inflammation

That could let researchers develop a new and better way to stop inflammation. “Small molecules are perhaps more affordable as treatments and can hit things like this ion channel switch, TRPM7,” said researcher Michael Schappe, a graduate student in Desai’s lab. “We could use that to address inflammation in a bunch of contexts, but particularly in instances like neuroinflammation, where [current] treatments are particularly ineffective.”

Desai noted that drug companies are already at work on drugs that could target this type of switch. And that could be good news for patients with many inflammatory diseases.

“Right now, you have conditions like arthritis or IBD [inflammatory bowel disease], where inflammation plays a huge role. They do have very good drugs for them, but these drugs are extremely expensive and cannot be taken orally by the patients. They can cost as much as $20,000 a year,” he said. “The reason for that is that they’re biologicals. They’re protein molecules that are very difficult to make and distribute. But having identified an ion channel as a target in this context allows you to use small molecules, which are ridiculously cheap compared to biologicals and can be taken orally by the patients.”

The discovery of the new drug target, the researchers noted, was made possible by something very unusual about UVA. To learn more, visit the Making of Medicine blog at https://makingofmedicine.virginia.edu/2018/02/26/the-switch-that-could-shut-down-inflammation-even-in-the-brain/

Findings Published

The researchers have published their findings in the scientific journal Immunity. The study’s authors were Schappe, Kalina Szteyn, Marta E. Stremska, Suresh K. Mendu, Taylor K. Downs, Philip V. Seegren, Michelle A. Mahoney, Sumeet Dixit, Julia K. Krupa, Eric J. Stipes, Jason S. Rogers, Samantha E. Adamson, Norbert Leitinger and Desai.

The research was supported by the National Institutes of Health, grants GM108989 and 5T32GM007055-41.