A new study shows how Cour Pharmaceuticals‘ nanoparticle platform is able to modulate immune system activity, lending support for the company’s experimental treatments.
Cour’s CNP-106, an experimental treatment for generalized myasthenia gravis, is currently being tested in a Phase 1b/2a clinical trial (NCT06106672), which may still be enrolling participants at sites in the U.S.
The study, “STING/type I interferon pathway is required for antigen-containing PLGA nanoparticle- and apoptotic cell–induced CD4+ T cell tolerance,” was published in Science Advances. It was funded in part by Cour and by the National Institutes of Health.
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Autoimmune disorders like MG are a breakdown of immune tolerance
Myasthenia gravis is an autoimmune disorder — a disease caused by the immune system mistakenly attacking the body’s own healthy tissue as if it were an infectious threat. Specifically, in MG, immune cells make antibodies that disrupt the communication between nerve cells and muscles. The most common type of MG-driving antibodies target a muscle protein called the acetylcholine receptor (AChR).
Autoimmune disorders like MG are fundamentally a breakdown of immune tolerance — the process by which the immune system distinguishes between healthy parts of the body and infectious threats. Cour’s platform uses nanoparticles to restore tolerance, essentially retraining the immune system so it stops mistaking healthy parts of the body for a threat. For example, CNP-106 aims to retrain the immune system not to attack the AChR protein.
“Although many current treatments for autoimmune diseases rely on broad immune suppression, the immune system itself has evolved precise mechanisms to maintain tolerance to self. These new findings reinforce [Cour nanoparticles] as a unique and potent technology for the antigen-specific treatment of autoimmune diseases while preserving normal immune function,” Adam Elhofy, PhD, vice president of research at Cour and co-author of the study, said in a company press release.
In the study, scientists reported on experiments that shed light on exactly how Cour’s nanoparticles work at the molecular level. The researchers found that the nanoparticles are taken up by immune cells called myeloid cells, which then undergo apoptosis (programmed cell death). This in turn activates a molecular signaling pathway known as the stimulator of interferon genes (STING)/type I interferon pathway, ultimately leading to increased levels of regulatory T-cells (Tregs), which are immune cells critical for maintaining tolerance.
These findings establish that [Cour nanoparticle]-induced tolerance recapitulates the physiological mechanism by which the immune system establishes and maintains self-tolerance during the continual turnover of [blood] cells.
The researchers found that these same molecular mechanisms are also at play in the spleen, where healthy blood cells frequently die off. In other words, the nanoparticles seem to replicate the mechanisms the immune system normally relies on to maintain tolerance.
“Importantly, the study shows that immune tolerance induced by [the death of healthy blood cells in the spleen] depends on the STING/type I interferon pathway,” said Stephen D. Miller, PhD, co-author of the study and co-inventor of Cour’s nanoparticle platform at Northwestern University. “These findings establish that [Cour nanoparticle]-induced tolerance recapitulates the physiological mechanism by which the immune system establishes and maintains self-tolerance during the continual turnover of [blood] cells.”
