Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Research Breakthrough Selectively Represses the Immune System

Published: Thursday, March 21, 2013
Last Updated: Thursday, March 21, 2013
Bookmark and Share
NIH-funded scientists develop new treatment to combat autoimmune disease in mouse model.

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.

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."

In addition to a grant from NIBIB (R01-EB013198-02), the research was also supported by NIH's National Institute of Neurological Disorders and Stroke (NS026543), the Myelin Repair Foundation, and the Juvenile Diabetes Research Foundation (17-2011-343).

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,600+ scientific posters on ePosters
  • More Than 3,800+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

NIH Grantees Win 2015 Nobel Prize in Chemistry
The 2015 Nobel Prize in chemistry has been awarded to NIH grantees Paul Modrich, Ph.D., of the Howard Hughes Medical Institute and the Duke University School of Medicine, Durham, N.C.; and Aziz Sancar, M.D., Ph.D., of the University of North Carolina, Chapel Hill, N.C.,.
Thursday, October 08, 2015
NIH Announces High-Risk, High-Reward Research Awardees
NIH to fund 78 awards to support highly innovative biomedical research.
Wednesday, October 07, 2015
New Gene Therapy for Vision Loss From a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Tuesday, October 06, 2015
NIH Funding Targets Gaps in Biomedical Research
New awards support emerging issues in cutting-edge biomedical research fields.
Tuesday, October 06, 2015
Scientists Test New Gene Therapy for Vision Loss from a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Tuesday, October 06, 2015
Dormant Viral Genes May Awaken to Cause ALS
NIH human and mouse study may open an unexplored path for finding treatments.
Thursday, October 01, 2015
Scientists Create World’s Largest Catalog of Human Genomic Variation
An international team of scientists from the 1000 Genomes Project Consortium has created the world’s largest catalog of genomic differences among humans, providing researchers with powerful clues to help them establish why some people are susceptible to various diseases.
Thursday, October 01, 2015
Drug Used To Treat HIV Linked to Lower Bone Mass in Newborns
NIH study finds mothers’ use of tenofovir tied to lower bone mineral content in babies.
Wednesday, September 30, 2015
Repairing Nerve Pathways With 3-D Printing
A novel 3-D printing approach was used to create custom scaffolds that helped damaged rat nerves regenerate and improved the animals’ ability to walk.
Tuesday, September 29, 2015
Bone Risks Linked to Genetic Variants
A large-scale genomic study uncovered novel genetic variants and led researchers to an unexpected gene that affects bone density and fracture risk.
Tuesday, September 29, 2015
Genetic Adaptations to Diet and Climate
Researchers found genetic variations in the Inuit of Greenland that reflect adaptations to their specific diet and climate.
Tuesday, September 29, 2015
NIH Launches Landmark Study On Substance Use And Adolescent Brain Development
Thirteen grants awarded to look at cognitive and social development in approximately 10,000 children.
Monday, September 28, 2015
Grants to Help Identify Variants in the Genome’s Regulatory Regions
New computational approaches needed to wade through millions of inherited DNA differences to find which ones matter.
Thursday, September 24, 2015
Grants Awarded to Explore the Genome’s Regulatory Regions that Affect Disease Risk
New computational approaches needed to wade through millions of inherited DNA differences to find which ones matter.
Tuesday, September 22, 2015
NIH Framework Points The Way Forward For Developing The President’s Precision Medicine Initiative
The NIH Advisory Committee to the Director has presented to NIH Director Francis S. Collins, M.D., Ph.D., a detailed design framework for building a national research participant group, called a cohort, of 1 million or more Americans to expand our knowledge and practice of precision medicine.
Monday, September 21, 2015
Scientific News
Genetic Defences of Bacteria Don’t Aid Antibiotic Resistance
Genetic responses to the stresses caused by antibiotics don’t help bacteria to evolve a resistance to the medications, according to a new study by Oxford University researchers.
Detecting HIV Diagnostic Antibodies with DNA Nanomachines
New research may revolutionize the slow, cumbersome and expensive process of detecting the antibodies that can help with the diagnosis of infectious and auto-immune diseases such as rheumatoid arthritis and HIV.
Snapshot Turns T Cell Immunology on its Head
New research may have implications for 1 diabetes sufferers.
Tolerant Immune System Increases Cancer Risk
Researchers have found that individuals with high immunoCRIT ratios may have an increased risk of developing certain cancers.
Developing a Gel that Mimics Human Breast for Cancer Research
Scientists at the Universities of Manchester and Nottingham have been funded to develop a gel that will match many of the biological structures of human breast tissue, to advance cancer research and reduce animal testing.
Cell's Waste Disposal System Regulates Body Clock Proteins
New way to identify interacting proteins could identify potential drug targets.
New Approach to Treating Heparin-induced Blood Disorder
A potential treatment for a serious clotting condition that can strike patients who receive heparin to treat or prevent blood clots may lie within reach by elucidating the structure of the protein complex at its root.
Horse Illness Shares Signs of Human Disease
Horses with a rare nerve condition have similar signs of disease as people with conditions such as Alzheimer’s, a study has found.
How a Molecular Motor Untangles Protein
Diseases such as Alzheimer’s, Parkinson’s and prion diseases, all involve “tangled” proteins.
Compound Doubles Up On Cancer Detection
Researchers have found that tagging a pair of markers found almost exclusively on a common brain cancer yields a cancer signal that is both more obvious and more specific to cancer.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos