In osteoarthritis, the M1/M2 balance in the macrophage population is correlated with disease severity. Reprogramming macrophages from M1 to M2 by inducing efferocyctosis is being considered as a treatment option. Various groups are looking at functionalized nanoparticles and biologics like aptotic monocytes for injection into an affected joint such as an OA affected knee. I am trying to understand how much efferocytosis can be expected to be induced in an OA knee if OA macrophage efferocytosis rates are compromised. Is the compromise in all members of the population in that they are each simply slower to be induced to phagocytosis (e.g., of aptotic monocytes), or is it that a portion of the population is rendered incapable of phagocytosis? Can an injection of monocytes induced to aptosis be expected to correct the imbalance? How long-lived would that effect be?

There has been a positively reported open label Ph 1 trial, but a limiting factor in evaluating knee injection therapies is the very high placebo effect for subjective measurements such as WOMAC or self reported pain. The upcoming release of double-blinded Ph 2 trial results would be the first such test of the efficacy of macrophage reprogramming through efferocytosis. Unfortunately, the trial does not appear to include M1/M2 assessments or other objective measures of inflammation.