Past Incubator Program awardee, Christopher Ritchlin, M.D., M.P.H., Professor and Chief of Allergy/Immunology and Rheumatology in the Department of Medicine at URMC, has just won a $2.5 million grant from the National Institutes of Health to explore a promising biomarker and possible drug target of psoriatic arthritis (PsA).
Approximately 650,000 people in the US are affected by PsA, which occurs when the body’s immune system mistakenly attacks its own skin and joint cells causing painful skin plaques and inflammation of joints and tendons. In addition, nearly half of all PsA patients experience erosion of the bone in their affected joints, which is caused by overabundance of bone-chewing cells, called osteoclasts.
In previous studies funded by the CTSI Incubator Program Award, Ritchlin and his collaborators began to shed light on how and why osteoclasts run amok in PsA.
They zeroed in on a protein called DC-STAMP, which is expressed at high levels in cells that fuse together to form osteoclasts. When they inhibited DC-STAMP with an antibody, osteoclasts could no longer form. They also found that certain PsA drugs caused a drop in DC-STAMP when patients experienced symptom relief.
In their new grant, Ritchlin and his collaborators plan to explore how DC-STAMP fosters formation of osteoclasts using an innovative technique called optogenetics to activate DC-STAMP with light and observe what happens downstream. They will also explore whether inhibiting DC-STAMP can reduce inflammation of joints and bone damage in PsA and if it can be used to predict which PsA patients will respond to current therapies.
Initial results from the grant have highlighted the necessity of thorough investigations of disease mechanisms. While Ritchlin and his collaborators originally showed that DC-STAMP fosters early steps of osteoclast formation leading to bone erosion, new data suggests it may actually inhibit at later stages.
Ritchlin credits the Incubator Program for setting this work in motion by “bringing people together who normally don’t work together, in a unique environment to explore questions of importance to cell biology and medicine.”