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PostPosted: Wed Nov 21, 2012 7:18 pm    Post subject: Nanoparticles stop MS in mice Reply with quote

From Medical News Today, November 19, 2012:

Quote:
Nanoparticles Stop Multiple Sclerosis In Mice
Patient / Public: 4.44 (43 votes)

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.

...

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 [that] 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 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


The entire article can be seen here.
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PostPosted: Sun Nov 03, 2013 2:12 pm    Post subject: "Big MS breakthrough" Reply with quote

From Northwestern University News, June 2013:

Quote:
BIG MULTIPLE SCLEROSIS BREAKTHROUGH

by Marla Paul

CHICAGO --- A phase 1 clinical trial for the first treatment to reset the immune system of multiple sclerosis (MS) patients showed the therapy was safe and dramatically reduced patientsí immune systemsí reactivity to myelin by 50 to 75 percent, according to new Northwestern Medicine research.

In MS, the immune system attacks and destroys myelin, the insulating layer that forms around nerves in the spinal cord, brain and optic nerve. When the insulation is destroyed, electrical signals canít be effectively conducted, resulting in symptoms that range from mild limb numbness to paralysis or blindness.

ďThe therapy stops autoimmune responses that are already activated and prevents the activation of new autoimmune cells,Ē said Stephen Miller, the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. ďOur approach leaves the function of the normal immune system intact. Thatís the holy grail.Ē

Miller is the co-senior author of a paper on the study, which was published June 5 in the journal Science Translational Medicine. The study is a collaboration between Northwesternís Feinberg School, University Hospital Zurich in Switzerland and University Medical Center Hamburg-Eppendorf in Germany.

The human trial is the translation of more than 30 years of preclinical research in Miller's lab.

In the trial, the MS patientsí own specially processed white blood cells were used to stealthily deliver billions of myelin antigens into their bodies so their immune systems would recognize them as harmless and develop tolerance to them.

Current therapies for MS suppress the entire immune system, making patients more susceptible to everyday infections and higher rates of cancer.

While the trialís nine patients -- who were treated in Hamburg, Germany -- were too few to statistically determine the treatmentís ability to prevent the progression of MS, the study did show patients who received the highest dose of white blood cells had the greatest reduction in myelin reactivity.

The primary aim of the study was to demonstrate the treatmentís safety and tolerability. It showed the intravenous injection of up to 3 billion white blood cells with myelin antigens caused no adverse affects in MS patients. Most importantly, it did not reactivate the patientsí disease and did not affect their healthy immunity to real pathogens.

As part of the study, researchers tested patientsí immunity to tetanus because all had received tetanus shots in their lifetime. One month after the treatment, their immune responses to tetanus remained strong, showing the treatmentís immune effect was specific only to myelin.

The human safety study sets the stage for a phase 2 trial to see if the new treatment can prevent the progression of MS in humans. Scientists are currently trying to raise $1.5 million to launch the trial, which has already been approved in Switzerland. Millerís preclinical research demonstrated the treatment stopped the progression of relapsing-remitting MS in mice.

ďIn the phase 2 trial we want to treat patients as early as possible in the disease before they have paralysis due to myelin damage.Ē Miller said. ďOnce the myelin is destroyed, itís hard to repair that.Ē

In the trial, patientsí white blood cells were filtered out, specially processed and coupled with myelin antigens by a complex GMP manufacturing process developed by the study co-senior authors, Roland Martin, Mireia Sospedra, and Andreas Lutterotti and their team at the University Medical Center Hamburg-Eppendorf. Then billions of these dead cells secretly carrying the myelin antigens were injected intravenously into the patients. The cells entered the spleen, which filters the blood and helps the body dispose of aging and dying blood cells. During this process, the immune cells start to recognize myelin as a harmless and immune tolerance quickly develops. This was confirmed in the patients by immune assays developed and carried out by the research team in Hamburg.

This therapy, with further testing, may be useful for treating not only MS but also a host of other autoimmune and allergic diseases simply by switching the antigens attached to the cells. Previously published preclinical research by Miller showed the therapyís effectiveness for type 1 diabetes and airway allergy (asthma) and peanut allergy.

The MS human trial relates directly to Millerís recently published research in mice in which he used nanoparticles -- rather than a patientís white blood cells -- to deliver the myelin antigen. Using a patientís white blood cells is a costly and labor-intensive procedure. Millerís study showed the nanoparticles, which are potentially cheaper and more accessible to a general population, could be as effective as the white blood cells as delivery vehicles. This nanoparticle technology has been licensed to Cour Pharmaceutical Development Company and is in preclinical development.

Millerís research represents several pillars of Northwesternís Strategic Plan by discovering new ways to treat disease in the biomedical sciences and translating those discoveries into ideas and products that make the world a better place for everyone.

___________________________

The research was supported by the German Federal Ministry for Education and Research and the Cumming Foundation.

- See more at: http://www.northwestern.edu/newscenter/stories/2013/06/big-multiple-sclerosis-breakthrough.html?utm_campaign#sthash.LCs5SNS4.dpuf


The article can be seen here.
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