Academic Journal
Main Category: Multiple Sclerosis
Also Included In: Biology / Biochemistry; Immune System / Vaccines
Article Date: 19 Nov 2012 - 3:00 PST
A breakthrough new experimental treatment that uses nanoparticles covered with proteins to trick the immune system, managed to stop it attacking myelin and halt disease progression in mice with relapsing remitting multiple sclerosis (MS). The researchers say the approach may also be applicable to other auto-immune diseases such as asthma and type 1 diabetes.
Corresponding author Stephen Miller is the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine in Chicago in the US. He says in a statement:
"We administered these particles to animals who have a disease very similar to relapsing remitting multiple sclerosis and stopped it in its tracks."
"We prevented any future relapses for up to 100 days, which is the equivalent of several years in the life of an MS patient," he adds.
The study results suggest the nanoparticles are as effective as using patients' own white blood cells to deliver the antigen, an approach that is being tested in a phase I/II trial in MS patients. Using nanoparticles would be much cheaper and easier, say the researchers.
Miller and colleagues report their study, which was funded by the Myelin Repair Foundation, the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (NIH), and the Juvenile Diabetes Research Foundation, in the 18 November online issue of Nature Biotechnology.
Multiple Sclerosis (MS)
An auto-immune disease is where the immune system mistakenly attacks healthy tissue as well as clearing away harmful pathogens and cell debris. The type of tissue it attacks gives rise to different diseases.In the case of Multiple Sclerosis (MS), the auto-immune target is myelin, the protein that forms the protective sheath that insulates nerve fibers in the brain, spinal cord and eyes and preserves the vital electrical signals they carry.
When the myelin is destroyed, the electrical signals can't travel, and the result is the characteristic symptoms of MS, which range from mild limb numbness to paralysis or blindness.
About 80% of MS patients have the relapsing remitting form of the disease, where there are periods of symptom flare-up (relapse) interspersed with periods where they stop (remit), either partially or completely.
Protein-Covered Biodegradable Nanoparticles Trick the Immune System
The researchers used biodegradable nanoparticles covered with myelin proteins or antigens to trick the immune system into treating myelin as "friendly". The nanoparticles are made from the same material as dissolvable stitches, except they are much smaller, about 200 times thinner than human hair.For their study, they injected the nanoparticles, bearing their myelin antigen cargo, into mice bred to develop a disease similar to the human form of relapsing remitting MS.
The particles travelled to the spleen, a key immune system organ that removes unwanted materials such as old and dying cells from the blood, makes new blood cells and stores blood platelets.
Once in the spleen, the particles were engulfed by macrophages, white blood cells that literally gobble up and digest pathogens and unwanted materials and then send signals to other immune cells to target those materials.
But the effect in this case was to make the immune system view the nanoparticles as ordinary dying blood cells and nothing to be concerned about. This created immune tolerance to the myelin antigen by directly inhibiting the myelin responsive T cells. It also increased the numbers of regulatory T cells and further calmed the autoimmune response.
"Resets" Rather than Shuts Down Immune System
An attractive feature of this study is it shows a potential therapy that does not suppress the whole immune system as do current therapies for MS, which make patients more vulnerable to everyday infections and put them at higher risk for cancer.Instead, the nanoparticles, with their myelin antigens, "reset" the immune system to normal. The result is it stops treating myelin as an alien invader and stops attacking it.
Christine Kelley, National Institute of Biomedical Imaging and Bioengineering director of the division of Discovery Science and Technology at the NIH, says:
"The key here is that this antigen/particle-based approach to induction of tolerance is selective and targeted. Unlike generalized immunosuppression, which is the current therapy used for autoimmune diseases, this new process does not shut down the whole immune system."
Biodegradable Material Is Already FDA Approved
The nanoparticles and Miller and colleagues used are made of a polymer called Poly(lactide-co-glycolide) (PLG), which comprises lactic acid and glycolic acid, both natural metabolites in the human body. PLG is most commonly used for biodegradable sutures or dissolvable stitches.Because PLG is already approved by the US Food and Drug Administration (FDA) for other uses, this should make it easier to get approval for using it to move this research from mice to human subjects.
The nanoparticles used in this study were developed by co-corresponding author Lonnie Shea, professor of chemical and biological engineering at Northwestern's McCormick School of Engineering and Applied Science.
The researchers tested different sizes of nanoparticles and found 500 nanometers was the best at resetting the immune response.
Potential for Treating Range of Auto-Immune Diseases
Miller says:"The beauty of this new technology is it can be used in many immune-related diseases. We simply change the antigen that's delivered."
Shea and Miller are currently testing the nanoparticles to treat type 1 diabetes and airway diseases such as asthma.
Nanoparticles offer an attractive alternative to other approaches: they can be readily produced in a laboratory and standardized for manufacturing. This suggests therapies based on these mateials would be cheaper and more accessible to a general population.
Scott Johnson, CEO, president and founder of the Myelin Repair Foundation, says:
"The overarching goal is to ensure this important therapeutic pathway has its best chance to reach patients, with MS and all autoimmune diseases."
Written by Catharine Paddock PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
Additional source: Northwestern University.
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Visitor Opinions (latest shown first)
fantastic news
posted by Kathy on 19 Nov 2012 at 7:53 amThis is fantastic news - on many fronts. The fact that it's utilizing lactic acid and glycolic acid, both natural metabolites in the human body is comforting to those of us introducing drugs into our systems constantly to try to suppress our immune response. The fact that its already approved by the FDA as sutures and has been used without incident is wonderful. Hopefully, that will speed this process along significantly. Add to all of that, it should be easily manufactured thereby driving down costs - an MS'er couldn't ask for more! Congrats to the Myelin Repair Foundation and all others who helped push this research forward. And, from all the FUMS'ers in the world - thank you.
CIDP
posted by Angela Tischler on 19 Nov 2012 at 6:25 amThis should work with CIDP as well. CIDP is so rare that it is mostly ignored.
A coming wave of effective autoimmune disease treatment
posted by Walter on 19 Nov 2012 at 5:05 amFor people with any autoimmune disorder, which includes a large number of disease, this development may be comparable in its impact to the discovery of pennicillin.
Another Step Forward
posted by DW Bergner on 19 Nov 2012 at 4:52 amWe're all ever hopeful for a cure. I've been cursed with MS since 1995 (misdiagnosed until 2006). I'm currently on Gilenya and Ampyra. I look forward to the day when I and my MS family are free from this painful disorder. I applaud all those researchers who work tirelessly for us. Keep up the GREAT work! To the mice, thanks, I appreciate your work too. I am sending this article to my doctor nephew and my biologist researcher niece. Again, KEEP UP THE GREAT WORK! GO ORANGE! (We wear orange for MS)
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