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Breakthrough nanoparticle halts multiple sclerosis
EurekAlert! ^ | 11/18/12 | Marla Paul

Posted on 11/21/2012 11:41:34 PM PST by LibWhacker

New nanotechnology can be used for Type 1 diabetes, food allergies and asthma

CHICAGO --- In a breakthrough for nanotechnology and multiple sclerosis, a biodegradable nanoparticle turns out to be the perfect vehicle to stealthily deliver an antigen that tricks the immune system into stopping its attack on myelin and halt a model of relapsing remitting multiple sclerosis (MS) in mice, according to new Northwestern Medicine research.

The new nanotechnology also can be applied to a variety of immune-mediated diseases including Type 1 diabetes, food allergies and airway allergies such as asthma.

In MS, the immune system attacks the myelin membrane that insulates nerves cells in the brain, spinal cord and optic nerve. When the insulation is destroyed, electrical signals can't be effectively conducted, resulting in symptoms that range from mild limb numbness to paralysis or blindness. About 80 percent of MS patients are diagnosed with the relapsing remitting form of the disease.

The Northwestern nanotechnology does not suppress the entire immune system as do current therapies for MS, which make patients more susceptible to everyday infections and higher rates of cancer. Rather, when the nanoparticles are attached to myelin antigens and injected into the mice, the immune system is reset to normal. The immune system stops recognizing myelin as an alien invader and halts its attack on it.

"This is a highly significant breakthrough in translational immunotherapy," said Stephen Miller, a corresponding author of the study and the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. "The beauty of this new technology is it can be used in many immune-related diseases. We simply change the antigen that's delivered."

"The holy grail is to develop a therapy that is specific to the pathological immune response, in this case the body attacking myelin," Miller added. "Our approach resets the immune system so it no longer attacks myelin but leaves the function of the normal immune system intact."

The nanoparticle, made from an easily produced and already FDA-approved substance, was developed by Lonnie Shea, professor of chemical and biological engineering at Northwestern's McCormick School of Engineering and Applied Science.

"This is a major breakthrough in nanotechnology, showing you can use it to regulate the immune system," said Shea, also a corresponding author. The paper will be published Nov. 18 in the journal Nature Biotechnology.

Miller and Shea are also members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. In addition, Shea is a member of the Institute for BioNanotechnology in Medicine and the Chemistry of Life Processes Institute.

CLINICAL TRIAL FOR MS TESTS SAME APPROACH -- WITH KEY DIFFERENCE

The study's method is the same approach now being tested in multiple sclerosis patients in a phase I/II clinical trial -- with one key difference. The trial uses a patient's own white blood cells -- a costly and labor intensive procedure -- to deliver the antigen. The purpose of the new study was to see if nanoparticles could be as effective as the white blood cells as delivery vehicles. They were.

THE BIG NANOPARTICLE ADVANTAGE FOR IMMUNOTHERAPY

Nanoparticles have many advantages; they can be readily produced in a laboratory and standardized for manufacturing. They would make the potential therapy cheaper and more accessible to a general population. In addition, these nanoparticles are made of a polymer called Poly(lactide-co-glycolide) (PLG), which consists of lactic acid and glycolic acid, both natural metabolites in the human body. PLG is most commonly used for biodegradable sutures.

The fact that PLG is already FDA approved for other applications should facilitate translating the research to patients, Shea noted. Miller and Shea tested nanoparticles of various sizes and discovered that 500 nanometers was most effective at modulating the immune response.

"We administered these particles to animals who have a disease very similar to relapsing remitting multiple sclerosis and stopped it in its tracks," Miller said. "We prevented any future relapses for up to 100 days, which is the equivalent of several years in the life of an MS patient."

Shea and Miller also are currently testing the nanoparticles to treat Type one diabetes and airway diseases such as asthma.

NANOPARTICLES FOOL IMMUNE SYSTEM

In the study, researchers attached myelin antigens to the nanoparticles and injected them intravenously into the mice. The particles entered the spleen, which filters the blood and helps the body dispose of aging and dying blood cells. There, the particles were engulfed by macrophages, a type of immune cell, which then displayed the antigens on their cell surface. The immune system viewed the nanoparticles as ordinary dying blood cells and nothing to be concerned about. This created immune tolerance to the antigen by directly inhibiting the activity of myelin responsive T cells and by increasing the numbers of regulatory T cells which further calmed the autoimmune response.

"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," said Christine Kelley, National Institute of Biomedical Imaging and Bioengineering director of the division of Discovery Science and Technology at the National Institutes of Health, which supported the research. "This collaborative effort between expertise in immunology and bioengineering is a terrific example of the tremendous advances that can be made with scientifically convergent approaches to biomedical problems."

"We are proud to share our expertise in therapeutics development with Dr. Stephen Miller's stellar team of academic scientists," said Scott Johnson, CEO, president and founder of the Myelin Repair Foundation. "The idea to couple antigens to nanoparticles was conceived in discussions between Dr. Miller's laboratory, the Myelin Repair Foundation's drug discovery advisory board and Dr. Michael Pleiss, a member of the Myelin Repair Foundation's internal research team, and we combined our efforts to focus on patient-oriented, clinically relevant research with broad implications for all autoimmune diseases. Our unique research model is designed to foster and extract the innovation from the academic science that we fund and transition these technologies to commercialization. The overarching goal is to ensure this important therapeutic pathway has its best chance to reach patients, with MS and all autoimmune diseases."


TOPICS: News/Current Events
KEYWORDS: asthma; autoimmune; diabetes; immunesystem; immunology; mice; mouse; ms; multiple; multiplesclerosis; nanoparticle; nanoparticles; nanotechnology; sclerosis

1 posted on 11/21/2012 11:41:41 PM PST by LibWhacker
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To: LibWhacker

If this works perhaps it can also be used to turn off the breast cancer BRCA markers.


2 posted on 11/22/2012 12:01:31 AM PST by fella ("As it was before Noah, so shall it be again,")
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To: LibWhacker

I wonder if it might just effective against Alzheimer’s disease?


3 posted on 11/22/2012 12:11:21 AM PST by SatinDoll (NATURAL BORN CITZEN: BORN IN THE USA OF CITIZEN PARENTS.)
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To: fella
Very good news. There are a lot of autoimmune diseases that may benefit from this technology.

On the down side, if the immune response can be turned off, it can probably be turned on. Biological mischief, or warfare, could become undetectable, gradual, and masked as a genetic disease vs a pathogen.

4 posted on 11/22/2012 12:13:48 AM PST by uncommonsense (Conservatives believe what they see; Liberals see what they believe.)
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To: LibWhacker

We.are.Borg.

You.will.be.ass.imi.la.ted.

Re.sis.tance.is.fu.tile.

Sorry, couldn’t help it.
:)


5 posted on 11/22/2012 12:23:08 AM PST by Westbrook (Children do not divide your love, they multiply it.)
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To: LibWhacker

I wonder if this could be used for organ transplants, too.


6 posted on 11/22/2012 12:40:43 AM PST by Moonman62 (The US has become a government with a country, rather than a country with a government.)
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To: LibWhacker

ping


7 posted on 11/22/2012 1:17:57 AM PST by nikos1121
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To: fella

fibromyalgia, meniere’s, MD, many others one would think. often the messenger is worse than the disease though.


8 posted on 11/22/2012 2:34:35 AM PST by GailA (those who do not keep promises to Military, won't keep them to U)
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To: LibWhacker

Thank you SCIENCE!!! Amazing work!


9 posted on 11/22/2012 2:53:07 AM PST by mporter345
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To: LibWhacker

Ok boys and girls, name another country that will fund research and developement of new, cutting edge medical advancements and breakthroughs once the American version of national health care is in full swing. The formula for success is ObamaCare = cost savings = NO Care.


10 posted on 11/22/2012 3:24:42 AM PST by Artie (We are surrounded by MORONS)
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To: GailA

CF, Coeliac, ...... Lupus ~ these are all pretty miserable conditions.


11 posted on 11/22/2012 4:17:50 AM PST by muawiyah
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To: Artie
ObamaKKKare has already reduced funding at the CDC for research into epidemics ~ epidemiology. A discussion on CSPAN the other day indicated it's down to less than 10% of what it was under George Bush.

That's going to be the future of medicine in this country ~ you'll be lucky to get stitches in open wounds, or aspirin at a drugstore.

12 posted on 11/22/2012 4:19:59 AM PST by muawiyah
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To: LibWhacker

bttt


13 posted on 11/22/2012 4:41:15 AM PST by steelyourfaith (Expel the Occupy White House squatters !!!)
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To: LibWhacker

Medical ping.


14 posted on 11/22/2012 4:45:13 AM PST by Chainmail (A simple rule of life: if you can be blamed, you're responsible.)
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To: muawiyah
ObamaKKKare has already reduced funding at the CDC for research into epidemics ~ epidemiology.

Spoke to a PHD research type that writes and looks for the grants for this stuff @ a College of Medicine. She noted Drug Companies are not spending their Capital anymore for Researching Drugs. They wait for the Colleges, CDC, etc to come up with something that may make a stage trial and they they might dip their toe in the water. I don't know when this all changed, I think it happened even prior to the crash of 2008.

Now with Obamacare on top it is a Double FUBAR....

15 posted on 11/22/2012 5:18:20 AM PST by taildragger (( Tighten the 5 point harness and brace for Impact Freepers, ya know it's coming..... ))
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To: rdb3

Ping


16 posted on 11/22/2012 5:23:34 AM PST by Incorrigible (If I lead, follow me; If I pause, push me; If I retreat, kill me.)
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To: Incorrigible

That would be nice! Tysabri is working very well for me, though.


17 posted on 11/22/2012 2:31:55 PM PST by rdb3 (We're all going to get what only some of us deserve...)
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To: Incorrigible

That would be nice! Tysabri is working very well for me, though.


18 posted on 11/22/2012 2:32:08 PM PST by rdb3 (We're all going to get what only some of us deserve...)
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To: Incorrigible

That would be nice! Tysabri is working very well for me, though.


19 posted on 11/22/2012 2:32:21 PM PST by rdb3 (We're all going to get what only some of us deserve...)
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To: rdb3

I told my wife she could become Borg!


20 posted on 11/22/2012 4:13:56 PM PST by Incorrigible (If I lead, follow me; If I pause, push me; If I retreat, kill me.)
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To: Moonman62; LibWhacker; austinmark; FreedomCalls; IslandJeff; JRochelle; MarMema; Txsleuth; ...
I wonder if this could be used for organ transplants, too.

No way if you're talking about a transplant from any Tom, Dick or Harry. They would be foreign bodies in the biologic sense of the term. You have to prevent graft versus host disease and host versus graft disease. Unless it is an identical antigenic match, the immunosuppresion required can leave anyone vulnerable to otherwise harmless microbes like AIDS patients.

This story is about turning off an animal's autoimmune attack upon itself using antigens from myelin, the latter being the substance of what gives that color to vertebrates' central nervous system "white matter."

Here's the meat of the press relelease:

In the study, researchers attached myelin antigens to the nanoparticles and injected them intravenously into the mice. The particles entered the spleen, which filters the blood and helps the body dispose of aging and dying blood cells. There, the particles were engulfed by macrophages, a type of immune cell, which then displayed the antigens on their cell surface. The immune system viewed the nanoparticles as ordinary dying blood cells and nothing to be concerned about. This created immune tolerance to the antigen by directly inhibiting the activity of myelin responsive T cells and by increasing the numbers of regulatory T cells which further calmed the autoimmune response.

"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," said Christine Kelley...

Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis

FReepmail me if you want on or off the diabetes ping list.

If this pans out in humans for MS, it could work for type 1 diabetes and latent autoimmune diabetes in adults among other autoimmune diseases.

P.S. There's no mystery about these nano/microparticles. It's just polymer chemistry with the normal products of mammalian metabolism.

21 posted on 11/26/2012 3:28:47 PM PST by neverdem ( Xin loi min oi)
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To: CatDancer

Check this story. It could translate to type 1 diabetes if they can use the right antigen or antigens.


22 posted on 11/26/2012 5:16:24 PM PST by neverdem ( Xin loi min oi)
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