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).
NIBIB's mission is to support multidisciplinary research and research training at the crossroads of engineering and the biological and physical sciences. NIBIB supports emerging technology research and development within its internal laboratories and through grants, collaborations, and training. More information is available at the NIBIB website: http://www.nibib.nih.gov/.
NINDS is the nation's leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease – a burden borne by every age group, by every segment of society, by people all over the world.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.
Margot Kern | EurekAlert!
Further reports about: > Gates Foundation > NIBIB > NIH > T-cell > animal models > autoimmune disease > autoimmune disorders > blood cell > brain cell > health services > immune response > immune system > immunosuppressant drug > medical research > mouse model > multidisciplinary research > natural mechanism > white blood cell
Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.
The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
23.03.2018 | Event News
19.03.2018 | Event News
16.03.2018 | Event News
23.03.2018 | Materials Sciences
23.03.2018 | Agricultural and Forestry Science
23.03.2018 | Physics and Astronomy