For Immediate Release
Monday, Nov 19, 2012
Contact:
Margot Kern
nibibpress@mail.nih.gov
301-496-3500
Please see below for media coverage of the release
Research breakthrough selectively represses the immune system
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 Discovery 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).
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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 (http://www.ninds.nih.gov) 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.
NBCNews article
Last Updated On 11/28/2012