NK1R

AMSTERDAM, Sept. 26, 2024. Psoriasis, a chronic skin condition affecting over 6 million people in Europe, is characterized by rapid skin cell production, leading to scaling and inflammation. While it has long been suspected that stress plays a role in exacerbating psoriasis, this research offers conclusive evidence of this link. In the study, psoriatic lesions were induced in healthy human skin xenografts on mice (n=25) through the injection of autologous, in vitro IL-2-preactivated peripheral blood mononuclear cells. After achieving lesion remission with topical dexamethasone, the mice were exposed to either sonic (sound) or sham stress for 24 hours. The recurrence of psoriatic lesions was then tracked over the following 14 days. Remarkably, sonic stress led to a relapse of psoriatic lesions in all human skin xenografts within 14 days. This was accompanied by significant changes in psoriasis-related skin phenomena, including increased epidermal thickness, K16 expression, keratinocyte proliferation, anti-microbial peptide expression, and immune activation of intraepidermal cells. Further analysis showed that sonic stress significantly increased immune cell presence in the skin and elevated proinflammatory mediators. Additionally, neurogenic inflammation biomarkers were upregulated. Sonic stress also led to elevated levels of tryptase, indicating mast cell activation, and increased expression of NK-1R, the receptor for substance P (SP). "Psychoemotional stress triggers the release of proinflammatory neuropeptides like SP, leading to neurogenic skin inflammation by activating immune cells, particularly through mast cell degranulation," explains Professor Amos Gilhar, lead researcher of the study. "This is further amplified by corticotropin-releasing hormone (CRH) and NGF, which heighten inflammation and promote keratinocyte hyperproliferation, thereby triggering and worsening psoriatic lesions in susceptible individuals." The research team also tested the efficacy of aprepitant, an FDA-approved anti-emetic neurokinin-1 receptor (NK1-R) antagonist, in preventing stress-induced psoriasis relapse. Aprepitant prevented relapse in 80% of cases and normalised most inflammatory markers. "Aprepitant shows great promise as a potential therapy for stress-induced psoriasis exacerbations," Professor Gilhar remarks, though he cautioned about its off-label use and the need for further safety data. "Aprepitant selectively targets the SP-induced component of neurogenic inflammation but doesn't impact other mediators like NGF and CRH. Combining NK-1R antagonists with other treatments may prove more effective." Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

Innovative research has provided compelling evidence that perceived stress can directly trigger the relapse of psoriatic skin lesions. The study, presented today at the EADV Congress 2024, is the first to scientifically validate this connection in vivo. AMSTERDAM, Sept. 26, 2024 /PRNewswire/ -- Psoriasis, a chronic skin condition affecting over 6 million people in Europe, is characterised by rapid skin cell production, leading to scaling and inflammation. While it has long been suspected that stress plays a role in exacerbating psoriasis, this research offers conclusive evidence of this link. In the study, psoriatic lesions were induced in healthy human skin xenografts on mice (n=25) through the injection of autologous, in vitro IL-2-preactivated peripheral blood mononuclear cells. After achieving lesion remission with topical dexamethasone, the mice were exposed to either sonic (sound) or sham stress for 24 hours. The recurrence of psoriatic lesions was then tracked over the following 14 days. Remarkably, sonic stress led to a relapse of psoriatic lesions in all human skin xenografts within 14 days. This was accompanied by significant changes in psoriasis-related skin phenomena, including increased epidermal thickness, K16 expression, keratinocyte proliferation, anti-microbial peptide expression, and immune activation of intraepidermal cells. Further analysis showed that sonic stress significantly increased immune cell presence in the skin and elevated proinflammatory mediators. Additionally, neurogenic inflammation biomarkers were upregulated. Sonic stress also led to elevated levels of tryptase, indicating mast cell activation, and increased expression of NK-1R, the receptor for substance P (SP). "Psychoemotional stress triggers the release of proinflammatory neuropeptides like SP, leading to neurogenic skin inflammation by activating immune cells, particularly through mast cell degranulation," explains Professor Amos Gilhar, lead researcher of the study. "This is further amplified by corticotropin-releasing hormone (CRH) and NGF, which heighten inflammation and promote keratinocyte hyperproliferation, thereby triggering and worsening psoriatic lesions in susceptible individuals." The research team also tested the efficacy of aprepitant, an FDA-approved anti-emetic neurokinin-1 receptor (NK1-R) antagonist, in preventing stress-induced psoriasis relapse. Aprepitant prevented relapse in 80% of cases and normalised most inflammatory markers. "Aprepitant shows great promise as a potential therapy for stress-induced psoriasis exacerbations," Professor Gilhar remarks, though he cautioned about its off-label use and the need for further safety data. "Aprepitant selectively targets the SP-induced component of neurogenic inflammation but doesn't impact other mediators like NGF and CRH. Combining NK-1R antagonists with other treatments may prove more effective." WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

In the hippocampus, one of the first brain regions usually damaged by Alzheimer’s disease, both 20-mg and 40-mg doses of Hoth Therapeutics' HT-ALZ reduced the percentage of astrocyte coverage compared to the control, according to the company. Much of the brain is made up of a constellation of star-shaped cells called astrocytes, which play vital roles in immunity, neuron maintenance and many other functions. In Alzheimer’s disease, some astrocytes serve as celestial guardians that break down the amyloid beta protein plaques that build up in the brain; others, however, go rogue, actually secreting amyloid beta themselves.A drug candidate from Hoth Therapeutics, based on the anti-nausea agent aprepitant, reduced the brain area covered by astrocytes and improved cognitive function in a mouse model of Alzheimer’s, the company announced in a Sept. 17 release.“The reductions in astrocyte activity and the corresponding improvements in cognitive function observed with HT- ALZ give us confidence as we move forward in our development process,” Hoth CEO Robb Knie said in the release.In the hippocampus, one of the first brain regions usually damaged by Alzheimer’s, both 20-mg and 40-mg doses of HT-ALZ reduced the percentage of astrocyte coverage compared to the control, the company said. A similar pattern was seen in the cortex, and the decrease in astrocytes corresponded with improved cognitive function, according to Hoth. HT-ALZ’s active ingredient is aprepitant, a molecule that binds to the neurokinin 1 receptor in the central nervous system and has been approved by the FDA since 2003. Aprepitant is sold by Merck as Emend to prevent nausea and vomiting in cancer patients undergoing chemotherapy.The reactive astrocytes that respond to Alzheimer’s and other diseases tend to be larger than normal astrocytes. In addition to some astrocytes secreting amyloid beta, the reactive cells also produce toxic byproducts as they work to break down amyloid beta into urea, which contributes to disease progression.Hoth is currently exploring whether treatment with HT-ALZ changes the size or total number of astrocytes, the company said. Early evidence suggests treated mice have fewer reactive astrocytes than control mice, the biotech said.HT-ALZ is being developed as an oral soluble film, according to Hoth’s website.