Currents: Eczema

Understanding Mechanical Itch

Scientists at Scripps Research have identified a protein in sensory nerves that works as a key detector of the “mechanical” itch stimulus of crawling insects, wool fibers, or other irritating objects that touch the skin.

The discovery, published last month in Nature, is the first identification of a sensor for mechanical itch rather than chemically-triggered itch, and it could lead to better treatments for itch conditions, such as eczema and psoriasis.

“These findings help us untangle the complexity of itch sensation, and suggest that PIEZO1 inhibitors could be very useful clinically,” says study senior author Ardem Patapoutian, PhD, a professor in the Department of Neuroscience at Scripps Research.

PIEZO1’s role in mechanical itch was unexpected. These unique, propeller-shaped “mechanosensor” ion channels are embedded in the outer membranes of many cell types. They become activated when mechanically distorted, opening their ion channels and triggering various downstream events. Since 2010, Patapoutian and colleagues have shown that PIEZO2 is a key mechanosensor for light touch via nerves in various tissues and organs. By contrast, the researchers have found that PIEZO1 has a variety of non-sensory roles throughout the body.

While initial studies suggested that PIEZO1 was not expressed in sensory neurons, recent investigations have suggested that it is expressed at low levels in some subsets of these neurons. In the new study, researchers followed up on this lead.

In experiments in mice, researchers confirmed that PIEZO1 is expressed, and appears to be a functional, mechanical pressure-sensitive ion channel protein in two types of sensory neuron that were already implicated in chemical itch. They also found PIEZO1-blocking compound alleviates scratching behaviors in mice with the equivalent of eczema.

The absence or enhancement of PIEZO1 activity caused at least a small reduction or increase of scratching due to chemical itch triggers—implying that mechanical and chemical itch signals may be transmitted in some cases by the same sensory neurons.

The researchers are now investigating the PIEZO1 gene in the human population.

One Year Data for Lebrikizumab for AD

Eighty percent of lebrikizumab responders maintained improvements in skin clearance and atopic dermatitis disease severity at 52 weeks with once every two week and once every four week maintenance dosing, according to topline results from the Phase 3 clinical trials (ADvocate 1 and 2).

Additionally, patients treated with lebrikizumab maintained itch relief across the two trials over the one-year period.

Lilly plans to submit a Biologics License Application to FDA for lebrikizumab in AD in the second half of this year.

Dupixent Approved for Young Children

FDA has approved Regeneron Pharmaceuticals, Inc. and Sanofi’s Dupixent (dupilumab) for children aged 6 months to 5 years with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

WATCH NOW

From biologics to JAK inhibitors to an exciting pipeline, there are so many options to target AD. Peter A. Lio, MD also discusses the potential benefits of using gentler adjunctive therapies like botanicals and naturals as part of an overall treatment plan.