Navigation Links
Research breakthrough selectively represses the immune system
Date:11/18/2012

Reporters, please see "For news media only" box at the end of the release for embargoed sound bites of researchers.

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 myelinthe insulating material that encases nerve fibers and facilitates electrical communication between brain cells.

Autoimmune disorders occur when T-cellsa type of white blood cell within the immune systemmistake 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-cellswhich recognize and have the potential to attack the body's healthy tissuesfrom 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-antigenstiny portions of proteins from the dying cellto 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."


'/>"/>

Contact: Margot Kern
nibibpress@mail.nih.gov
301-496-3500
NIH/National Institute of Biomedical Imaging & Bioengineering
Source:Eurekalert

Related biology news :

1. Notre Dame research could improve sustainability and cost effectiveness of wastewater treatment
2. USDA funded research leads to key discoveries in the pig genome
3. Dartmouth research: The clocks are ticking and the climate is changing
4. A class of RNA molecules protects germ cells from damage, Penn vet researchers show
5. Researchers sequence swine genome, discover associations that may advance animal and human health
6. Researchers uncover some good news for BCs troubled salmon populations
7. Researchers use GPS tracking to monitor crab behavior
8. University of Michigan, Michigan State University award grants for Great Lakes climate change research
9. GW Research chosen as paper of the week for blood coagulation discovery
10. Researchers tap into CO2 storage potential of mine waste
11. NIH awards Penn scientists $10 million over 5 years for innovative research on single cells
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/24/2016)... 24, 2016 Ampronix facilitates superior patient care by providing unparalleled technology to ... display is the latest premium product recently added to the range of products distributed ... ... ... Imaging- LCD Medical Display- Ampronix News ...
(Date:5/20/2016)... -- VoiceIt is excited to announce its new marketing ... working together, VoiceIt and VoicePass will offer an ... slightly different approaches to voice biometrics, collaboration between ... Both companies ... "This marketing and technology partnership allows VoiceIt ...
(Date:5/16/2016)... , May 16, 2016   EyeLock LLC , ... announced the opening of an IoT Center of Excellence ... and expand the development of embedded iris biometric applications. ... level of convenience and security with unmatched biometric accuracy, ... identity aside from DNA. EyeLock,s platform uses video technology ...
Breaking Biology News(10 mins):
(Date:5/26/2016)... ... ... After several promising treatments in Panama using stem cell ... in Panama, a 6 year-old Duchenne’s muscular dystrophy patient received his first umbilical ... approval of a second application for a single patient, investigational new drug (IND) ...
(Date:5/26/2016)... ... May 26, 2016 , ... ... today announced several positive developments that position the Company for the future. ... the transaction, Craig F. Kinghorn has been appointed Chairman of the Board, Curtis ...
(Date:5/26/2016)... ... May 26, 2016 , ... ... are used in leading laboratories all over the globe. Their cute firefly logo ... to manufacturing awesome cuvettes, FireflySci makes spectrophotometer calibration standards that never require recalibration. ...
(Date:5/25/2016)... ... May 25, 2016 , ... Lajollacooks4u has become a rising hotspot for specialized ... of its top attractions. Fortune 500 companies, such as Illumina, Hewlett-Packard, Qualcomm and ... intimate team-building experience. , Each event kicks off with an olive oil and salt-tasting ...
Breaking Biology Technology: