April 18, 2016
Ann Arbor – In an entirely new approach to treating asthma and allergies, a biodegradable nanoparticle acts like a Trojan horse, hiding an allergen in a friendly shell to convince the immune system not to attack it, according to new research from the University of Michigan and Northwestern University. As a result, the allergic reaction in the airways is shut down long term and an asthma attack prevented.
The technology can be applied to food allergies as well. The nanoparticle is currently being tested in a mouse model of peanut allergy, similar to food allergy in humans.
“Small quantities of allergen have been used to de-sensitize patients, and that delivering the allergen using emerging nanotechnologies can provide a more efficient and effective system” said senior author Lonnie Shea, the William and Valerie Hall Chair and Professor of Biomedical Engineering at the University of Michigan and adjunct professor at Northwestern.
The treatment can be applied to any allergy simply by loading the nanoparticle with the target allergen – from ragweed pollen to peanut protein.
In addition, the treatment makes use of an already FDA-approved material; the nanoparticles are composed of PLGA, a biopolymer that includes lactic acid and glycolic acid.
When the loaded nanoparticle is injected into the bloodstream of mice, the immune system sees the particle as innocuous debris. Then the nanoparticle and its hidden cargo are consumed by a macrophage, essentially a vacuum-cleaner cell.
“The vacuum-cleaner cell presents the allergen to the immune system in a way that says, ‘No worries, this belongs here,’” said Stephen Miller, another senior author on the study and the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. The immune system then shuts down its attack on the allergen, and the immune system is reset to normal.
The allergen, in this case egg protein, was administered into the lungs of mice who had been pretreated to be allergic to the protein and already had antibodies in their blood against it. After being treated with the nanoparticle, however, they no longer had an allergic response to the allergen.
The approach creates a more normal, balanced immune system by increasing the number of regulatory T cells – immune cells important for recognizing the airway allergens as normal – while turning off the allergy-causing Th2 T cells.
It’s the first time this method for creating tolerance in the immune system has been used in allergic diseases. The approach has been used in autoimmune diseases including multiple sclerosis and celiac disease in previous preclinical research at Northwestern, and a clinical trial using the nanoparticles to treat celiac disease is in development.
“The findings represent a novel, safe and effective long-term way to treat and potentially ‘cure’ patients with life-threatening respiratory and food allergies,” said Miller.
The asthma allergy study was in mice, but the technology is progressing to clinical trials in autoimmune disease. The nanoparticle technology is being developed commercially by Cour Pharmaceuticals Development Co. A clinical trial using the nanoparticles to treat celiac disease is in development.
More information: Biodegradable antigen-associated PLG nanoparticles tolerize Th2-mediated allergic airway inflammation pre- and postsensitization, PNAS, www.pnas.org/cgi/doi/10.1073/pnas.1505782113
The research was supported in part by grant EB-013198 from the National Institute of Biomedical Imaging and Bioengineering and grant NS-026543 from the National Institute of Neurological Disease and Stroke, both of the National Institutes of Health (NIH), the Dunard Fund and a predoctoral fellowship TL1R000108 from the NIH National Center for Research Resources and the National Center for Advancing Translational Sciences.