Neurogenic Inflammation

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

Incyte said Tuesday that it is bolstering its inflammation pipeline through a deal to acquire privately-held Escient Pharmaceuticals and its portfolio of oral mast cell antagonist programmes. The transaction will see Incyte pay $750 million plus Escient's remaining net cash balance at closing, expected in the third quarter.Escient launched in 2018 with $40 million in series A funding to pursue the therapeutic potential of G protein-coupled receptor-targeted drugs, including the novel family of Mas-related G-protein receptors (MRGPRs). It has since gone on to raise $77.5 million and $120 million in successive series B and C rounds.MRGPRs are chemosensory receptors found on both sensory nerve and immune cells located near each other in key barrier tissues such as the skin, airways and gastrointestinal (GI) tract. Neuro-immune overactivation plays a central role in various disorders, including urticaria, atopic dermatitis, asthma, and chronic conditions involving neurogenic inflammation and pain, making MRGPRs promising targets for treatment, Escient says.Launch opportunities starting in 2029Through the deal, Incyte acquires EP262, an antagonist of MRGPRX2, that is currently in Phase II testing for chronic spontaneous urticaria and atopic dermatitis. It is also in a Phase Ib study for chronic inducible urticaria. "By blocking the activation of mast cells by various neuropeptides, EP262 holds great promise across a broad range of mast-cell-mediated diseases, as a once-a-day oral treatment devoid of the immuno-/myelosuppressive effects observed with other therapies," Escient says on its website.The company's other lead programme EP547, which targets MRGPRX4, could help treat cholestatic pruritus and other conditions with severe pruritus. According to Escient, the drug may provide relief without the central nervous system and GI side effects often seen with other treatments."EP262 and EP547 are complementary additions to our portfolio, providing an opportunity to…address the needs of patients with inflammatory diseases and [add] potential launch opportunities starting in 2029," remarked Incyte CEO Hervé Hoppenot.