The first results have been revealed from Phase 2 human trials investigating a promising new treatment for celiac disease. The novel nanoparticle technology was found to significantly induce an immune tolerance to gluten in celiac subjects after just two intravenous treatments.
The treatment involves encapsulating a specific allergen inside a biodegradable nanoparticle. The human body responds innocuously to the presence of the nanoparticle, treating it like harmless debris, and sending an immune cell called a macrophage to clean it up. Macrophages have been euphemistically referred to as the body’s vacuum-cleaner cells, as they clear foreign substances from the body.
“The vacuum-cleaner cell presents the allergen or antigen to the immune system in a way that says, ‘No worries, this belongs here,’” explains Stephen Miller, who spent years developing the technology at Northwestern University. “The immune system then shuts down its attack on the allergen, and the immune system is reset to normal.”
In theory, the nanoparticle technology could be utilized to treat any number of autoimmune diseases triggered by specific known antigens, but this first exploration for the technology has focused on celiac disease. The current trial involves loading the nanoparticle with a molecule called gliadin, an essential protein in gluten known to trigger inflammatory responses in celiac disease patients.
This Phase 2 trial is small, involving only 34 patients, but it offers the first evidence of efficacy in human subjects. The prospective treatment involves two intravenous administrations of the nanoparticles, one week apart. Seven days after the second treatment the subjects were challenged with 12 grams (0.4 oz) of gluten per day for three days, and then six grams (0.2 oz) of gluten each day for the next 11 days. The majority of the subjects tolerated the gluten challenge following the nanoparticle treatment, showing an impressive 90 percent reduction in inflammatory markers compared to an untreated control group.
The treatment has been granted a Fast Track designation from the U.S. Food and Drug Administration, allowing it to expediently move through Phase 2 and 3 human trials. Takeda Pharmaceutical Company has also announced a US$420 million global license acquisition of the prospective treatment, signaling confidence in its efficacy despite several years of trials still ahead before the technology moves into clinical applications.
While this first deployment of the technology is focusing on gluten and celiac disease, Stephen Miller suggests the nanoparticle can be loaded with other compounds targeting a number of autoimmune conditions.
“This is the first demonstration the technology works in patients,” says Miller. “We have also shown that we can encapsulate myelin into the nanoparticle to induce tolerance to that substance in multiple sclerosis models, or put a protein from pancreatic beta cells to induce tolerance to insulin in type 1 diabetes models.”
Source: Northwestern University