Approach Could Target Malfunctioning Immune Response While Preserving Patients’ Ability to Fight Other Illnesses
Immune system cells, shown in orange, wrongly attack the myelin sheaths that protect nerve cells, shown in blue. New UMD research opens up new pathways to "turn off" this harmful immune response, which leads to motor problems and other neurological issues, while preserving rest of the immune system to fight disease.
University of Maryland bioengineers have identified a method that could help slow or reverse multiple sclerosis without compromising a patient’s immune system, one of the chief drawbacks of existing treatments.
Their results, published this month in the journal ACS Nano, represent a new milestone in their efforts to design an immunotherapy strategy to treat MS and other autoimmune diseases.
MS afflicts nearly 2.5 million people worldwide, causing their immune systems to wrongfully attack myelin, the insulation that surrounds and protects nerve fibers in the brain and spinal cord. This results in damaged nerve fibers and cells, leading to a loss of motor function and other neurological complications.
Current therapies for MS decrease the activity of the overall immune system to restrain the detrimental “attack,” but at a cost that leaves MS patients vulnerable to certain infections or illnesses, including some cancers.
Instead of this non-specific approach to treatment, Fischell Department of Bioengineering (BIOE) Minta Martin Professor of Engineering and U.S. Department of Veterans Affairs (VA) Research Biologist Christopher Jewell and members of his Immune Engineering Lab are exploring ways to “turn off” only the harmful immune attack that occurs during MS, while leaving healthy functions of the immune system intact.
“MS is an awful disease that causes a slow debilitation in patients,” Jewell said. “It’s also a disease that is very costly to patients and their families, both financially and in quality of life. We need more effective treatments that are safe and easy to take. Immunotherapies that integrate new technologies to direct and retrain the immune system could enable the ultimate goal of specific and long-lasting therapies.”
The team has been working with specially designed nanomaterials built in an innovative way, using immune signals as the only building blocks. They hope this unique design can be used to reprogram how the immune system responds to the body’s own healthy cells—or “self” cells—in the brain and spinal cord during MS.
Funded by a $1.1 million VA award, Jewell and his team found inspiration in how our bodies typically respond to infection. Recent studies have shown that some of the defense mechanisms our bodies typically use to fight infection—such as those known as toll-like receptors—go haywire during autoimmune disease and become overactive in MS.
Jewell and his team decided to target these pathways to block inflammation, hypothesizing that by eliminating harmful cues while delivering helpful myelin self-molecules, they could create an opportunity to retrain self-reactive T cells, which attack myelin, to instead become regulatory T cells. These special immune cells enable more specific control of the cells that do damage during MS or other autoimmune diseases, without suppressing the function of normal cells.
“This was a very exciting outcome to us—we discovered that the immunotherapeutics we designed reversed paralysis in a pre-clinical model of MS that mimics the terrible bouts of relapse and remission patients experience,” Jewell said. “This occurred even when we waited to begin treatment until the peak of disease onset.”
Next, Jewell and his team made a bold move: they introduced foreign antigens to see if the immunotherapy they invented caused immunosuppression.
The results were groundbreaking: The research team observed mice in the experiment had normal immune response to the foreign antigens, measuring two core types of immune functions—both antibodies and T cells; this occurred despite the fact that the mice had received immunotherapy treatment to combat the attack of myelin.
“The ability of vaccines to eliminate specific targets has transformed the fight against viral and bacterial infections,” said Jewell Lab postdoctoral researcher Robert “Smitty” Oakes, first author of the ACS Nano paper and a VA Career Development awardee. “Achieving this goal of antigen-specific tolerance for MS would revolutionize patient care, similar to how vaccines and checkpoint blockade have revolutionized infectious disease and cancer treatments, respectively.”
In addition to Jewell and Oakes, former National Science Foundation (NSF) graduate fellow Lisa Tostanoski Ph.D. ’17 and current NSF graduate fellow Eugene Froimchuk, Assistant Research Scientist Senta Kapnick and researchers Sheneil Black and Xiangbin Zeng contributed to the paper.
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