NGF

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

Nicole Bean for BioSpace With promising early results, cell and gene therapies are making headway against both rare and common ocular and auditory diseases. Eyes and ears. Two of our most critical sensory organs yet usually taken for granted—until something goes wrong. But while largely ignored by busy individuals and most insurance plans, biopharma R&D—specifically cell and gene therapy—is paying attention. Let’s start with hearing. The human ear is made up of three different parts: the outer ear, middle ear and inner ear—a complex structure offering many opportunities for something to go wrong. Hearing Loss Breakthroughs This spring, Regeneron made headlines when it announced that the investigational gene therapy DB-OTO improved hearing in two young children with “profound genetic deafness” since birth, with one patient returning to normal hearing levels within six months of treatment. In this case, the children’s hearing loss was due to a deficiency in otoferlin, a protein expressed in the hair cells of the inner ear. Regeneron’s gene therapy delivers a functioning copy of the gene to the inner ear, stimulating otoferlin production. Eli Lilly subsidiary Akouos and Fudan University in Shanghai and Mass Eye and Ear have also enjoyed early success with otoferlin gene therapies . Of course, these therapies will only help the 1% to 8% of patients afflicted by this particular genetic mutation. However, according to the American Hearing Research Foundation , about 75% of congenital deafness has a genetic cause, indicating the potential for more gene therapies. Although I can hear perfectly well, hearing loss is a condition with which I am quite familiar. My grandfather was born deaf. He never knew the cause but, today, he could have had his DNA tested and had the hope of a treatment on the horizon. Ocular CGT Advances On the ocular side, cell and gene therapies are making progress against more common diseases like wet age-related macular degeneration (AMD), a leading cause of blindness, as well as dry eye syndrome (DED)—and here my interest is even more personal. Four years ago, I began to experience a scratchy, gritty sensation in my eyes. This quickly graduated to a burning, sandpaper-dry condition that makes everyday tasks—like driving a car or staring at a computer screen—challenging. I’m far from the only one dealing with these issues. I’ve commiserated with at least two colleagues, which isn’t surprising as DED affects around one in 11 people worldwide, according to the NIH. After exhausting the first tier of treatments—such as prescription eye drops, omega-3 fatty acids, intense pulsed light therapy and scleral contact lenses—I learned about a cellular therapy called amniotic membrane treatment . Extracted from the innermost layer of the human placenta, amniotic membrane is full of neurotrophic factors such as nerve growth factor, collagen and basal epithelial cells. It also contains unique anti-inflammatory, anti-fibrotic and pro-healing properties that can help ease conditions like DED, corneal neuropathic pain, graft versus host disease and post-corneal transplants, according to an article published in Ocular Surface . A 2018 study found that 74 of 84 patients enjoyed an improved ocular surface and a “notable” reduction in symptom severity after just over a week of treatment with amniotic membrane. As with many therapies, it doesn’t always work the first time; 10% of eyes in this study required repeated treatment, and I personally am on my second round. Interestingly, this study breaks the data down by individual eyes, as patients did not always have the same response in both eyes. I have so far experienced slightly better results in my right eye from this second round of treatment. Companies are also making progress on the gene therapy side, specifically for wet AMD . REGENXBIO and AbbVie, Adverum and 4D Molecular Therapeutics have all seen positive results from their investigative gene therapies for this condition, which affects around 1.5 million people in the U.S. alone—a far bigger patient population than current rare disease gene therapies target. The mechanism for these wet AMD treatments is also different from traditional gene therapies, which work by repairing or replacing a faulty disease-causing gene. For wet AMD, investigational gene therapies deliver the coding sequence for the therapeutic molecule to the eye, which serves as a biofactory to produce the medicine. This could ease the treatment burden of the multiple injections currently required to treat the disease. Several other companies, including AbbVie and Capsida Biotherapeutics , Kriya Therapeutics and SpliceBio , are developing gene therapies to treat thyroid eye disease, inherited retinal disease and more. Having been treated with one of these therapies, I can also attest to the fact that they are not cheap. But progress is being made. While gene therapies for rare diseases that correct or replace a faulty gene can carry a multi-million-dollar price tag, experts say the cost of the wet AMD treatments currently in development will be much lower. There is definitely a ray of light and a joyful noise on the horizon.