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November 19, 2012

Nanoparticles Stop Multiple Sclerosis In Mice and could treat food allergies, asthma and other autoimmune diseases

NBC News - Researchers trying to find a way to treat multiple sclerosis think they’ve come up with an approach that could not only help patients with MS, but those with a range of so-called autoimmune diseases, from type-1 diabetes to psoriasis, and perhaps even food allergies.

So far it’s only worked in mice, but it has worked especially well. And while mice are different from humans in many ways, their immune systems are quite similar.

“If this works, it is going to be absolutely fantastic,” said Bill Heetderks, who directs outside research at the National Institute of Biomedical Imaging and Bioengineering, part of the National Institutes of Health, which helped pay for the research. “Even if it doesn’t work, it’s going to be another step down the road.”

Web MD - In multiple sclerosis, the body attacks its own myelin. Like the insulation around electric wires, myelin is a material that coats nerve fibers, allowing them to effectively carry signals that power the body.

Nature Biotechnology - Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyeliti



Over time, people with MS may develop a host of problems related to myelin damage, including trouble with muscle coordination, movement, numbness, pain, and vision problems. About 80% of people with MS have the relapsing-remitting form. The mice in this study were bred to have this type of MS.

Researchers wondered if they could stop that process by making use of the body's "garbage disposal system." In addition to protecting the body from foreign invaders, an important role of the immune system is getting rid of dead cells.

When dead or dying cells pass through the spleen, big white blood cells called macrophages gobble them up. As part of this process the macrophages send signals to other parts of the immune system, letting them know that the dying cells aren't dangerous, just routine bits of trash that need to go.

Years ago, researcher Stephen D. Miller, PhD, an immunologist in the Feinberg School of Medicine at Northwestern University in Chicago, figured that it might be possible to hijack this garbage removal system and get the body to recognize -- and then ignore -- proteins it was mistaking for threats.

The researchers used on poly(lactide-co-glycolide), or PLG. It's a material that's used to make sutures, grafts, and other things that are meant to slowly dissolve in the body. By first dissolving PLG and then spinning the watery solution very rapidly, they were able to make tiny particles that could carry myelin proteins.

When they infused these protein-coated particles into the mice, they were able to both prevent the development of a mouse disease that mimics MS and to stop attacks in mice that already had the disease.

"We think this is actually a simpler option. You don't have to manipulate cells and put an antigen on them. This way, you could have an off-the-shelf product," Shea says.

What's more, the nanoparticles can be coated in many different kinds of proteins, which means they could one day treat other kinds of autoimmune diseases and even problems like food allergies.

"There are just so many possible applications of this, it's fun to think about," says Shea.

First, though, the technology has to be tested in humans. Before that can happen, Miller says they need to conduct more animal trials. If all goes well, he thinks the first human studies might be two years away.

ABSTRACT - Aberrant T-cell activation underlies many autoimmune disorders, yet most attempts to induce T-cell tolerance have failed. Building on previous strategies for tolerance induction that exploited natural mechanisms for clearing apoptotic debris, we show that antigen-decorated microparticles (500-nm diameter) induce long-term T-cell tolerance in mice with relapsing experimental autoimmune encephalomyelitis. Specifically, intravenous infusion of either polystyrene or biodegradable poly(lactide-co-glycolide) microparticles bearing encephalitogenic peptides prevents the onset and modifies the course of the disease. These beneficial effects require microparticle uptake by marginal zone macrophages expressing the scavenger receptor MARCO and are mediated in part by the activity of regulatory T cells, abortive T-cell activation and T-cell anergy. Together these data highlight the potential for using microparticles to target natural apoptotic clearance pathways to inactivate pathogenic T cells and halt the disease process in autoimmunity

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