Emory University researchers have discovered a family of enzymes that show promise in treating IgG-mediated autoimmune diseases, including myasthenia gravis (MG). The study, published in Cell, highlights the therapeutic potential of an endoglycosidase enzyme called CU43 in managing immune-related disorders.
CU43 Enzyme Reduces IgG-Mediated Pathologies
Myasthenia gravis is a chronic autoimmune disorder characterized by antibodies blocking communication between nerves and muscles, leading to muscle weakness, double vision, and breathing difficulties. Many autoimmune diseases and other human illnesses result from the dysregulation of IgG antibodies, collectively referred to as IgG-mediated pathologies. The Emory team's research focused on identifying enzymes capable of modifying antibodies to mitigate these disease-causing effects.
According to Eric Sundberg, principal investigator and biochemistry researcher at Emory University's School of Medicine, "Human antibodies, although critically important for mounting an immune response to pathogens and fighting disease, sometimes cause disease themselves – including autoimmune diseases. The enzymes we discovered can modify antibodies in such a way that they no longer cause disease."
Superior Efficacy Compared to Existing Treatments
The researchers tested the newly discovered enzyme in mouse models of several IgG-mediated pathologies. The results indicated that CU43 was highly effective in reducing disease symptoms. Notably, CU43 demonstrated significantly greater potency compared to existing MG treatments. The study found that 4,000 times less of the enzyme was needed to achieve the same biological effect. This enhanced potency could translate to fewer side effects and more flexible administration options for patients.
Jeffrey Ravetch, immunologist at Rockefeller University and co-author of the paper, commented, "The potency of this enzyme is quite remarkable when compared to current treatments for autoimmune diseases and thus warrants consideration for further development of the treatment for this important class of diseases."
Next Steps: Clinical Trials
The research team is now focused on translating these findings into clinical trials. "We hope to leverage these promising results in mice to move this enzyme rapidly into clinical trials in humans," says Sundberg. "It could potentially be used to treat a wide range of autoimmune diseases and other IgG-mediated pathologies."
The study's findings suggest that CU43 could represent a significant advancement in the treatment of autoimmune diseases, offering a more effective and potentially safer alternative to current therapies.
