New nanoparticle halts multiple sclerosis, now being tested in Type 1 diabetes and asthma

Nov 18, 2012

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 , food allergies and airway allergies such as asthma.

In MS, the attacks the membrane that insulates nerves cells in the brain, spinal cord and . When the insulation is destroyed, can't be effectively conducted, resulting in symptoms that range from mild limb numbness to paralysis or blindness. About 80 percent of 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 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 ," 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 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."

Explore further: Crystallizing the DNA nanotechnology dream: Scientists have designed the first large DNA crystals

More information: Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis, Nature Biotechnology (2012) doi:10.1038/nbt.2434, www.nature.com/nbt/journal/vao… nt/abs/nbt.2434.html

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User comments : 19

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RealScience
5 / 5 (4) Nov 18, 2012
"The beauty of this new technology is it can be used in many immune-related diseases. We simply change the antigen that's delivered."

"Our approach resets the immune system so it no longer attacks myelin but leaves the function of the normal immune system intact."


If those statements both hold up, then this is huge - auto-immune diseases like MS, Type-1 diabetes, arthritis, etc. could be cured.
It is also likely that it could be used to prevent rejection of transplanted organs.
chromosome2
2.8 / 5 (4) Nov 18, 2012
My grandpa's mental state was great for his age until his immune system up and attacked his brain. I think he's on steroids now or something, he can at least make sense when he talks, but.. yeah.

My mom is gluten intolerant. If I understand correctly, this would help there too. But just *think*.. we're on the brink of a developed world without autoimmune disease, at the same time pot is being legalized AND bred to not contain THC, and full-genome and exome sequencing is getting faster and cheaper every month.. The face of death is changing. A world where everyone is forever young is a world where everyone is condemned to die suddenly, in their prime. Maybe it's the best way to go. I'm sure not going to turn down 150 or 200 years if it's offered me, but I really can't say if it'd be a good thing for our species..
Urgelt
1 / 5 (2) Nov 18, 2012
It's great progress; I hope human trials can start soon. But they may need to delve into alternative nanoparticle compounds. Seriously, you do not want to inject PLG into lactose-intolerant patients.
casualjoe
not rated yet Nov 18, 2012
This is excellent news and I hope this leads to the improvement of many peoples lives.
Shakescene21
5 / 5 (2) Nov 18, 2012
The main reason I read Physorg is learn about breakthroughs like this. What a rush!
My daughters have terrible asthma attacks. I hope this technology works in humans and becomes available asap.
Telekinetic
1 / 5 (4) Nov 18, 2012
The main reason I read Physorg is learn about breakthroughs like this. What a rush!
My daughters have terrible asthma attacks. I hope this technology works in humans and becomes available asap.

Why wait? Pycnogenol, an extract from French Maritime Pine bark has shown to be effective against asthma as well as quercitin, a non-citrus bioflavonoid. These are nature's answers to Merck and Eli Lilly. No side effects, either.
Mike_Massen
1 / 5 (3) Nov 18, 2012
In 2010 studied food science post grad at curtin uni in perth, Western Australia. Accessed high end peer reviewed journals on world databases to also study alzheimers, diabetes and parkinsons concluded:-

Most ppl on a western diet are deficient in Copper & likely molybdenum.

200 plus enzymes & proteins that compete *just* for copper, many are involved with fat metabolisation, insulin, immune system signalling & prion moderation ie Strong binding to copper.

Cause of MS has been correlated with Chlamydophila pneumoniae finds a place to survive in/near CSF pm me for video link, it is dissuaded by healthy copper intake. Also trials of a 3 antibiotic regime against the bacteria in MS sufferers have shown improvement some 2 years ago.

Since I have been on a high copper diet in conjunction with zinc (a co antagonist), manganese & magnesium, a major skin ailment from a maggot from Malaysian jungle in 1998 cleared up totally in 3weeks,

http://en.wikiped...n_health
Mike_Massen
1 / 5 (2) Nov 19, 2012
Telekinetic shared an interesting tidbit
..Pycnogenol, an extract from French Maritime Pine bark has shown to be effective against asthma as well as quercitin, a non-citrus bioflavonoid..
In relation to this is the use of various barka as flavourings for soups and casseroles in Britain for hundreds of years until late 1800's. Had anti-inflammatory properties, I understand they may have been salicylates. The same effect might be achieved by 100mg aspirin a day.

Please, re my last message, always check with a doctor, in a small proportion of ppl aspirin can cause stomach bleeds and make sure you don't have Wilson's disease re inappropriate metabolism re copper...

btw: My own doctor was under impression we can get enough copper from water pipes. Not true as within 3 months new pipes get a bio-film and/or silicates preventing copper leaching into water and the perception re copper being toxic is flawed for anything less than 10mg/day, most people hardly get 300 micrograms/day !

Just_some_guy
5 / 5 (1) Nov 19, 2012
It's great progress; I hope human trials can start soon. But they may need to delve into alternative nanoparticle compounds. Seriously, you do not want to inject PLG into lactose-intolerant patients.

Lactose intolerance is not an immune response. It is simply a lack of enzyme that breaks down lactose in the stomach and therefore it is instead broken down by bacteria in the lower intestines (with all the accompanying symptoms). The enzyme can be ingested prior to any such treatment. But I really doubt that it will be needed since this drug will be in the blood stream and not in the digestion system.
Shakescene21
not rated yet Nov 19, 2012
@Telekinetic. Thanks for the recommendation for quercitin and pycnogenol. Both of them are available for a reasonable price from my supplement provider. (It's a good thing they're not too expensive, because my HMO won't pay a nickel toward non-pharmaceuticals.)
antialias_physorg
5 / 5 (2) Nov 19, 2012
Looks like a pretty big deal, but I've seen too many animal studies that didn't translate to humans - so I'll just wait and see until the clinical studies are carried out (at least until they've passed phase II). Then I'll cheer for this.

The biodegradeable part of the nanoparticles is particularly important. Don't want nanoparticles accumulating in the liver/kidney until they pack it in.
Mike_Massen
1 / 5 (2) Nov 19, 2012
antialias_physorg offered observation
Looks like a pretty big deal, but I've seen too many animal studies that didn't translate to humans..
Indeed, the complexities of biochemistry.

Few yrs back with transgenic mice selected for early alzheimers. Feeding Cu organic complexes at high level in diet cleared up Amyloid-Beta42 type plaques *and* reversed their alzheimers 'completely'. Dose was still considerably below LD-50 & not considered toxic, I understand excipient was a powerful anti-emetic but, no human trials. Cu binds well to prions.

Interesting that human liver appears well adapted to high Cu levels, we need ~100ug/(Kg BodyWt)/day.

Most dont realise human fetus, in last trimester, absorbs as much Cu from the mother even to point of making mother dangerously deficient - until the fetus' liver has around 4 times the equivalent adult level of copper !

Mother's milk doesn't deliver much, Cu essential for many enzymes & proteins. Western food has negligible organic bound Cu.
antialias_physorg
5 / 5 (2) Nov 19, 2012
Dose was still considerably below LD-50 & not considered toxic

Stuff is considered toxic WAY below LD-50. The '50' simply means that at that dose 50% of the tested organisms die.
Mike_Massen
1 / 5 (1) Nov 19, 2012
Stuff is considered toxic WAY below LD-50. The '50' simply means that at that dose 50% of the tested organisms die.
Yes ! and the reason I offered is to explore huge variants not the same metric for all poisons. All good microbiologists and food chemists should appreciate the philosophy of Paracelcus Eg.
"All things are poison, and nothing is without poison; only the dose permits something not to be poisonous."

I have read of people randomly taking 100mg/day sporadic copper with only temporary effect of nausea and dizziness, no increased cancer risk and no long term liver damage.

Bile, from the liver, increases its lubricative properties with good consistent copper intakes. Unfortunately many copper salts including the organic variety such as gluconates are emetics.

The blue & slightly bitter mouth fresheners often use copper gluconate. Also chlorophyllin is a copper based food colouring agent produced by some plants, very strong soluble green but not particularly tasty.
wealthychef
not rated yet Nov 19, 2012
The main reason I read Physorg is learn about breakthroughs like this. What a rush!
My daughters have terrible asthma attacks. I hope this technology works in humans and becomes available asap.

I share your hope, but don't get too excited yet. Most things reported here have a fatal flaw in the ointment, like cost, or they only work on mice, or something that the authors don't mention. I am very hopeful of course, but physorg tends to do a LOT of uncritical cheerleading and not as much actual research from what I have seen. I'm not trying to put physorg down, they are fun to read, they just have room for improvement in that area.
jan_wal1
not rated yet Nov 19, 2012
could this be aplied to graves disease / leigh disease / melas ?
if you want to test it out, my wife and child have these diseases, we are desparate
Telekinetic
not rated yet Nov 19, 2012
could this be aplied to graves disease / leigh disease / melas ?
if you want to test it out, my wife and child have these diseases, we are desparate

So sorry for your plight. Unfortunately, this treatment is a long way off before they can test it on people. Try to find a naturopathic doctor in your area because they treat the system rather than the symptom. I can refer you to an M.D. that might be able to help if you send me a PM.
jan_wal1
5 / 5 (1) Nov 20, 2012
could this be aplied to graves disease / leigh disease / melas ?
if you want to test it out, my wife and child have these diseases, we are desparate

So sorry for your plight. Unfortunately, this treatment is a long way off before they can test it on people. Try to find a naturopathic doctor in your area because they treat the system rather than the symptom. I can refer you to an M.D. that might be able to help if you send me a PM.


ty for your sympathy, but we live in holland, ill go search for one around here :)

greets :)
Mike_Massen
1 / 5 (1) Nov 20, 2012
Please see my posts re diet and metalloid enzymes, low copper is implicated in failures of various paths of immune system signalling !

Try and find local data re copper/zinc content of your staple foods and get a blood test re serum copper etc...

ty for your sympathy, but we live in holland, ill go search for one around here :)
greets :)