Featured Research

from universities, journals, and other organizations

Scientists selectively repress immune system: New treatment to combat autoimmune disease in mouse model

Date:
November 18, 2012
Source:
NIH/National Institute of Biomedical Imaging & Bioengineering
Summary:
In a mouse model of multiple sclerosis (MS), researchers have developed innovative technology to selectively inhibit the part of the immune system responsible for attacking myelin -- the insulating material that encases nerve fibers and facilitates electrical communication between brain cells.

In a mouse model of multiple sclerosis (MS), researchers funded by the National Institutes of Health have developed innovative technology to selectively inhibit the part of the immune system responsible for attacking myelin -- the insulating material that encases nerve fibers and facilitates electrical communication between brain cells.

Related Articles


Autoimmune disorders occur when T-cells -- a type of white blood cell within the immune system -- mistake the body's own tissues for a foreign substance and attack them. Current treatment for autoimmune disorders involves the use of immunosuppressant drugs which tamp down the overall activity of the immune system. However, these medications leave patients susceptible to infections and increase their risk of cancer as the immune system's normal ability to identify and destroy aberrant cells within the body is compromised.

Supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) at NIH, Drs. Stephen Miller and Lonnie Shea at Northwestern University, Evanston, teamed up with researchers at the University of Sydney, and the Myelin Repair Foundation in Saratoga, Calif. to come up with a novel way of repressing only the part of the immune system that causes autoimmune disorders while leaving the rest of the system intact.

The new research takes advantage of a natural safeguard employed by the body to prevent autoreactive T-cells -- which recognize and have the potential to attack the body's healthy tissues -- from becoming active. They report their results in the Nov. 18 online edition of Nature Biotechnology.

"We're trying to do something that interfaces with the natural processes in the body," said Shea. "The body has natural mechanisms for shutting down an immune response that is inappropriate, and we're really just looking to tap into that."

One of these natural mechanisms involves the ongoing clearance of apoptotic, or dying, cells from the body. When a cell dies, it releases chemicals that attract specific cells of the immune system called macrophages. These macrophages gobble up the dying cell and deliver it to the spleen where it presents self-antigens -- tiny portions of proteins from the dying cell -- to a pool of T-cells. In order to prevent autoreactive T-cells from being activated, macrophages initiate the repression of any T-cells capable of binding to the self-antigens.

Dr. Miller was the first to demonstrate that by coupling a specific self-antigen such as myelin to apoptotic cells, one could tap into this natural mechanism to suppress T-cells that would normally attack the myelin. The lab spent decades demonstrating that they could generate antigen-specific immune suppression in various animal models of autoimmune diseases. Recently, they initiated a preliminary clinical trial with collaborators in Germany to test the safety of injecting the antigen-bound apoptotic cells into patients with MS. While the trial successfully demonstrated that the injections were safe, it also highlighted a key problem with using cells as a vehicle for antigen delivery:

"Cellular therapy is extremely expensive as it needs to be carried out in a large medical center that has the capability to isolate patient's white blood cells under sterile conditions and to re-infuse those antigen-coupled cells back into the patients," said Miller. "It's a costly, difficult, and time-consuming procedure."

Thus began a collaboration with Dr. Shea, a bioengineer at Northwestern University, to discuss the possibility of developing a surrogate for the apoptotic cells. After trying out various formulations, his lab successfully linked the desired antigens to microscopic, biodegradable particles which they predicted would be taken up by circulating macrophages similar to apoptotic cells.

Much to their amazement, when tested by the Miller lab, the antigen-bound particles were just as good, if not better, at inducing T-cell tolerance in animal models of autoimmune disorders.

Using their myelin-bound particles, the researchers were able to both prevent the initiation of MS in their mouse model as well as inhibit its progression when injected immediately following the first sign of clinical symptoms.

The research team is now hoping to begin phase I clinical trials using this new technology. The material that makes up the particles has already been approved by the U.S. Food and Drug Administration and is currently used in resorbable sutures as well as in clinical trials to deliver anti-cancer agents. Miller believes that the proven safety record of these particles along with their ability to be easily produced using good manufacturing practices will make it easier to translate their discovery into clinical use.

"I think we've come up with a very potent way to induce tolerance that can be easily translated into clinical practice. We're doing everything we can now to take this forward," said Miller.

In addition to its potential use for the treatment of MS, the researchers have shown in the lab that their therapy can induce tolerance for other autoimmune diseases such as type I diabetes and specific food allergies. They also speculate that transplant patients could benefit from the treatment which has the potential to retract the body's natural immune response against a transplanted organ. Dr. Christine Kelley, NIBIB director of the Division of Science and Technology, points to the unique collaboration between scientists and engineers that made this advance a reality.

"This discovery is testimony to the importance of multidisciplinary research efforts in healthcare," said Kelley. "The combined expertise of these immunology and bioengineering researchers has resulted in a valuable new perspective on treating autoimmune disorders."


Story Source:

The above story is based on materials provided by NIH/National Institute of Biomedical Imaging & Bioengineering. Note: Materials may be edited for content and length.


Journal Reference:

  1. Daniel R Getts, Aaron J Martin, Derrick P McCarthy, Rachael L Terry, Zoe N Hunter, Woon Teck Yap, Meghann Teague Getts, Michael Pleiss, Xunrong Luo, Nicholas JC King, Lonnie D Shea, Stephen D Miller. Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis. Nature Biotechnology, 2012; DOI: 10.1038/nbt.2434

Cite This Page:

NIH/National Institute of Biomedical Imaging & Bioengineering. "Scientists selectively repress immune system: New treatment to combat autoimmune disease in mouse model." ScienceDaily. ScienceDaily, 18 November 2012. <www.sciencedaily.com/releases/2012/11/121118141522.htm>.
NIH/National Institute of Biomedical Imaging & Bioengineering. (2012, November 18). Scientists selectively repress immune system: New treatment to combat autoimmune disease in mouse model. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2012/11/121118141522.htm
NIH/National Institute of Biomedical Imaging & Bioengineering. "Scientists selectively repress immune system: New treatment to combat autoimmune disease in mouse model." ScienceDaily. www.sciencedaily.com/releases/2012/11/121118141522.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

More Coverage


Breakthrough Nanoparticle Halts Multiple Sclerosis in Mice, Offers Hope for Other Immune-Related Diseases

Nov. 18, 2012 — In a breakthrough for nanotechnology and multiple sclerosis (MS), a biodegradable nanoparticle delivers an antigen that tricks the immune system and halts MS in mice. The approach, the first that ... read more

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins