Associate Professor University of Texas Medical Branch, Galveston Galveston, Texas, United States
Disclosure(s):
Ruksana Huda: No financial relationships to disclose
Introduction/Rationale: Muscle weakness and fatigue in autoimmune myasthenia gravis (MG) result from neuromuscular junction damage caused by autoantibody- and complement-mediated destruction of the acetylcholine receptor (AChR). In our ongoing efforts to develop a new and effective treatment for MG, we evaluated the effect of CD40 inhibition combined with duoconjugate treatments (BAFF receptor and B-cell maturation antigen-specific) in a mouse model of MG.
Methods: Conjugates consisted of target-specific siRNA linked to monoclonal antibodies that target pathogenic plasma cells and mature B cells. We evaluated this treatment using a Torpedo AChR/Complete Freund's Adjuvant-immunized mouse model of MG.
Results: Our research shows that conjugate treatment disrupts pathogenic B cells, reducing autoantibody levels and improving clinical outcomes. Additionally, combining CD40 with duoconjugates boosts treatment effectiveness, but only with specific combinations, not when used alone.
Conclusion: Our results suggest that CD40 inhibition, whether alone or in combination with other treatments, may not be effective for treating myasthenia gravis or other antibody-mediated autoimmune disorders.
