Rheumatoid Arthritis target

The Myeloid Inhibitory C-type Lectin like receptor (MICL) has a previously unexpected role in rheumatoid arthritis (RA). MICL has been shown to have involvement in regulation of the inflammatory response of myeloid cells during RA.

Studies with knock-out (MICL -/-) mice demonstrated that absence of MICL led to enhanced inflammation in a collagen antibody induced arthritis model. It was discovered that autoantibodies binding to MICL were responsible for myeloid cell activation. The addition of anti-MICL antibodies to an MICL wild type mouse restored the knockout disease phenotype. A small study of human patient samples revealed the presence of anti-MICL antibodies, suggesting a particular subset of rheumatoid arthritis patients where continuing presence of autoantibodies is exacerbating their condition by modulating myeloid cell activation. A patent has been filed covering potential diagnostic, prognostic and therapeutic approaches from identifying anti MICL antibodies and blocking the interaction with MICL while also developing screening systems for identifying novel RA treatments.

MICL is a C-type lectin receptor expressed predominantly by myeloid cells. It possesses a single extracellular C-type lectin domain that recognises endogenous ligand(s) and a cytoplasmic immunoreceptor tyrosine-based inhibitory motif that transduces intracellular inhibitory signals.

Applications

• As a novel mechanism for new therapeutic approaches to treatment of RA
• As a means of assessing, diagnosing or prognosing RA in patients
• As a way of evaluating disease progression or efficacy of treatment

Benefits

• Identification of a novel mechanism underlying disease perpetuation
• Diagnostic or prognostic testing
• Potential target for therapeutic intervention
• Stratification of RA patients
• Measurement of disease progression

A UK priority patent application has been filed (May 2014)