Targeting oncostatin M curbs chronic itch in mice

Reuters Health – 16/11/2021 - Targeting the cytokine oncostatin M (OSM) with an experimental inhibitor reduced inflammation and itch in mouse models of psoriasis and chronic itch, suggesting a similar approach might work in humans, researchers say.

"OSM was already known (to be) produced by the body's immune system, but previously its role in itch was unrecognized," Dr. Mark Hoon of the US National Institute of Dental and Craniofacial Research (NIDCR) in Bethesda told Reuters Health by email. "Experiments in mice showed how this factor dramatically exaggerated itch responses and studies that blocked its activity relieved itch in the animals."

"The next stage is to develop treatments that are safe in humans, and this requires additional work to find effective OSM blockers," he said. "Fortunately, while this research was going on at NIDCR, independently, pharmaceutical companies found such blockers, and have reported initiation of FDA-permitted investigational clinical trials that target OSM signaling."

"Results from these trials have yet to be published," he noted. "Until these results are reported, the effectiveness and safety of OSM treatments on itch remain unknown."

As reported in Science Translational Medicine, Dr. Hoon and colleagues analyzed sequencing data from skin biopsies and found that OSM was upregulated in the immune cells of patients with psoriasis, atopic dermatitis and cutaneous T cell lymphoma – all associated with chronic itch.

In vitro experiments showed that the OSM receptor (OSMR) is expressed by itch-selective natriuretic polypeptide B (Nppb) neurons, and that OSM is mainly produced by dermal T cells and monocytes. Notably, unlike many other pruritogens, OSM does not activate sensory neurons. Instead, it sensitizes neurons by potentiating neural responses to pruritogens and neural excitability.

In vivo data showed that OSM induced and exacerbated itchiness when injected into mice. However, in a mouse model of dermatitis, treatment with SC144, a molecule that indirectly inhibits OSM signaling, reduced itch behavior, suggesting that targeting OSM could be effective in reducing itch associated with inflammatory conditions.

The authors conclude, "Together, our results uncover OSM as an itch neuromodulator and reveal OSM signal transduction as a potential target for antipruritic therapy."

Dr. Adam Friedman, Professor and Chair of Dermatology at George Washington School of Medicine and Health Sciences in Washington DC, commented on the study in an email to Reuters Health. "More and more attention is being paid to OSM as an important T2 cytokine (of the IL-6 family) in the pathophysiology of chronic inflammatory diseases such as atopic dermatitis and, more recently, prurigo nodularis."

"The pivotal role in sensitizing neurons to pruritogens as demonstrated in the current study now underscores OSM and/or its signaling pathway as a key driver and orchestrator of itch. In fact, the efficacy of current drugs within our armamentarium may result from interference of this pathway, though more targeted approaches could enhance clinical outcomes. More research is needed to better understand the impact of disrupting OSM signaling to ensure both efficacy and safety."

SOURCE: https://bit.ly/3DiFBh7 Science Translational Medicine, online November 10, 2021.

By Marilynn Larkin



Posted on 16 November, 202123 November, 2021