MEK2

THURSDAY, Sept. 12, 2024 -- An ingredient in the hair dye a French woman used caused her to develop a vision-robbing retinopathy , researchers report. When she switched to a dye without these ingredients, called aromatic amines, her vision troubles resolved, according to a team led by Dr. Nicolas Chirpaz , an ophthalmologist at Edouard Herriot Hospital, in Lyon. Such cases could be rare, the researchers said, but spreading awareness of the danger "may allow prompt consideration to remove exposure to such hair dye" so eyes aren't permanently damaged, Chirpaz and colleagues said. They published their case report Sept. 12 in the journal JAMA Ophthalmology . As the French team noted, this isn't the first time hair dye has been linked to retinopathy: Three prior cases were reported in 2022 among "middle-aged women following exposure to hair dyes containing aromatic amines." In the latest case, a 61-year-old woman with no prior history of vision trouble came to doctors with progressively blurry vision in both eyes "a few days after dyeing her hair with hair dye containing aromatic amines," Chirpaz' group said. The aromatic amine in the dye used in this case was para-phenylenediamine. Upon examination, the woman was found to have multiple retinal detachments that resembled the damage that can occur in retinopathies that are tied to certain enzymes found in the eye, called MEK1 or MEK2. The woman's eyes also displayed an unhealthy "thickening of the neurosensory retina," the French team found. Tests were conducted to rule out a host of possible causes, including infections and even cancer. In the end, retinal damage caused by the ingredient in hair dye was "diagnosed based on the temporal association between symptoms and hair dye exposure," the team said. The woman soon switched her brand of hair dye, and her vision returned to 20/20 within a month. "Four years later, the patient reported using aromatic amines–free hair dye and has not experienced any recurrence," the study authors said. Chirpaz' team believes that aromatic amine chemicals such as para-phenylenediamine "disrupt" a neurochemical pathway that's essential to the health of what are known as retinal pigment epithelial cells. Cases of "retinopathy associated with the use of hair dye aromatic amines [RAHDAA]" remain rare, but doctors should be on the alert to the possibility when people show up with any retinopathy that doesn't have an easy explanation, the French team said. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

iStock, Nomadsoul1 Recursion’s oral drug candidate for cerebral cavernous malformation showed no improvements in patient- or physician-reported outcomes at 12 months. The biotech will engage with the FDA to determine the need for an additional study. Recursion on Tuesday released topline data from its Phase II SYCAMORE trial, showing that its drug candidate REC-994 is largely safe to use in patients with cerebral cavernous malformation—though its efficacy pro much to be desired. After 12 months of treatment, both 200-mg and 400-mg doses of REC-994 showed similar adverse event profiles to placebo, indicating that the investigational treatment is largely safe and tolerable for patients with cerebral cavernous malformation (CCM). However, SYCAMORE’s efficacy data were less promising. Magnetic resonance imaging showed a “trend toward reduced lesion volume” in patients who were given the higher, 400-mg dose of REC-994, compared with placebo. These trends improved over time, though Recursion reported no improvements in patient- or physician-reported outcomes at 12 months. Recursion Chief R&D and Commercial Officer Najat Khan in a statement said the biotech is “encouraged” by these findings, which make REC-994 “the first investigational therapy to demonstrate safety” in CCM, while also demonstrating “promising trends in exploratory efficacy endpoints.” “These results provide critical insights that will inform our next study design, including exploring study duration, higher doses, and a larger cohort of patients,” Khan said, noting that Tuesday’s readout “represents an early proof-of-platform milestone” for the biotech. Recursion is seeking a meeting with the FDA “as soon as practical” to determine the way forward for REC-994, including an additional clinical trial, according to the company. The biotech will also present findings from SYCAMORE at an upcoming scientific congress and will submit them for publication in a peer-reviewed journal. CCM is a rare neurovascular disease characterized by malformations of the spinal cord and the brain, often involving abnormally enlarged capillary cavities. The condition affects around 360,000 symptomatic patients, who are at heightened risk of seizures, headaches and progressive neurological deficits, as well as potentially fatal hemorrhagic strokes. There are currently no pharmacologic treatments for CCM. REC-994, an orally available small molecule superoxide scavenger, was discovered using Recursion’s AI-powered drug discovery platform, which leverages “one of the world’s largest proprietary biological and chemical datasets,” according to the biotech’s website . The platform then makes use of machine-learning algorithms to produce an extensive searchable list of interactions from this database. Recursion is also developing REC-2282, another orally available drug candidate that can penetrate the central nervous system, for the treatment of NF2-mutated meningiomas, and REC-4481, a non-ATP-competitive blocker of MEK1 and MEK 2 for familial adenomatous polyposis.

Dr. Brown is a world-leading expert in Neurofibromatosis (NF) and the Director of the Neurofibromatosis clinic at The Mount Sinai Hospital, NYMIAMI, Sept. 03, 2024 (GLOBE NEWSWIRE) -- Pasithea Therapeutics Corp. (NASDAQ: KTTA) (“Pasithea” or the “Company”), a clinical-stage biotechnology company developing PAS-004, a next-generation macrocyclic MEK inhibitor, for the treatment of neurofibromatosis type 1 (NF1) and other indications, announced today that Rebecca Brown, M.D., Ph.D. has been appointed as a member of the Company’s Scientific Advisory Board. Dr. Brown is currently Director of the Neurofibromatosis Clinic at The Mount Sinai Hospital and Assistant Professor in the Department of Neurology (Division of Neuro-Oncology), Internal Medicine, and Neurosurgery at the institution. Dr. Brown will contribute scientific insights and valuable clinical perspectives to Pasithea's development of PAS-004. Dr. Brown has been an investigator in dozens of NF1 research studies including basic, translational, and clinical trials, with a focus on cutaneous and plexiform neurofibromas in NF1. Her research has been published extensively in major scientific journals and regularly serves as faculty at national and international meetings. “We are honored to have Dr. Brown, an internationally recognized NF1 expert, join our Scientific Advisory Board,” commented Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea. “As we plan the initiation of our Phase 1/2a clinical trial in NF1 Dr. Brown’s extensive experience in the research and treatment of both plexiform and cutaneous neurofibromas will provide an important contribution to our PAS-004 development efforts going forward.” Dr. Rebecca Brown stated “I look forward to assisting with the development of PAS-004, a next-generation macrocyclic MEK inhibitor with promising preclinical data for the treatment of NF1.This product addresses an unmet need and potentially distinguishes itself from other drugs within the same class. The long half-life adds to other desirable features including a potentially superior therapeutic index, a cleaner safety profile, and easier compliance via once per day dosing. There have been tremendous achievements over the past 5 years in drug development for plexiform neurofibromas associated with NF1, and I believe that PAS-004 may provide the next big leap in treatment efficacy and compliance.” Dr. Rebecca Brown’s Biography Dr. Rebecca Brown (M.D., Ph.D.) is a board-certified adult neuro-oncologist who specializes in Neurofibromatosis (NF) and Schwannomatosis (SWN) genetic nerve tumor predisposition syndromes. She earned her Ph.D. from The University of Texas at Austin (UT Austin) in Neuroscience studying the molecular genomics and behavioral outcomes of endocrine-disrupting pollutants on females across multiple generations. Dr. Brown completed a post-doctoral fellowship at the Center for Strategic and Innovative Technologies at UT Austin in human performance research and then earned her M.D. from UT Southwestern in 2013. She completed her intern year at East Tennessee State University in 2014 and her neurology residency at Mount Sinai Hospital in NYC in 2017. She specialized in neuro-oncology during a fellowship at Memorial Sloan Kettering Cancer Center (MSKCC) completed in 2019. She worked as an instructor at MSKCC for 18 months prior to accepting a position as Assistant Professor and Director of the all-ages NF and SWN Clinic at The Mount Sinai Health System in January 2021. Dr. Brown has experience on both sides of the bench in NF laboratory research involving the RAS-RAF-MEK-ERK (MAPK) pathway, including genome editing, cell culture, xenografts, and clinical trials. Her particular interest is in developing treatments for NF1-associated dermal tumors called cutaneous neurofibromas. About PAS-004 PAS-004 is a small molecule allosteric inhibitor of MEK 1/2, which are dual-specificity protein kinases, in the MAPK signaling pathway. The MAPK pathway has been implicated in a variety of diseases, as it functions to drive cell proliferation, differentiation, survival, and a variety of other cellular functions that, when abnormally activated, are critical for the formation and progression of tumors, fibrosis, and other diseases. MEK inhibitors block phosphorylation (activation) of extracellular signal-regulated kinases (ERK), which can lead to cell death and inhibition of tumor growth. Existing FDA-approved MEK inhibitors are marketed for a range of diseases, including certain cancers and neurofibromatosis type 1 (NF1). We believe these MEK inhibitors suffer from certain limitations, including known toxicities. Unlike current FDA-approved MEK inhibitors, PAS-004 is macrocyclic, which we believe may lead to improved pharmacokinetic and safety (tolerability) profiles. Cyclization offers rigidity for stronger binding with drug target receptors. PAS-004 was designed to provide a longer half-life with what we believe is a better therapeutic window. Further, we believe the potency and safety profile that PAS-004 has demonstrated in preclinical studies may also lead to stronger and more durable response rates and efficacy, as well as better dosing schedules. PAS-004 has been tested in a range of mouse models of various diseases and has completed preclinical testing and animal toxicology studies. Additionally, PAS-004 has received orphan-drug designation from the FDA for the treatment of NF1, which may provide seven years of marketing exclusivity upon approval of an NDA. About Pasithea Therapeutics Corp. Pasithea is a clinical-stage biotechnology company focused on the discovery, research and development of innovative treatments for central nervous system (CNS) disorders and RASopathies. With an experienced team of experts in the fields of neuroscience, translational medicine, and drug development, Pasithea is developing new molecular entities for the treatment of neurological disorders, including Neurofibromatosis type 1 (NF1), Solid Tumors, and Amyotrophic Lateral Sclerosis (ALS). Forward Looking Statements This press release contains statements that constitute “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include all statements, other than statements of historical fact, regarding the Company’s current views and assumptions with respect to future events regarding its business, as well as other statements with respect to the Company’s plans, assumptions, expectations, beliefs and objectives, the success of the Company’s current and future business strategies, product development, preclinical studies clinical studies, clinical and regulatory timelines, market opportunity, competitive position, business strategies, potential growth opportunities and other statements that are predictive in nature. Forward-looking statements are subject to numerous conditions, many of which are beyond the control of the Company. While the Company believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to the Company on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties, including factors set forth in the Company’s most recent Annual Report on Form 10-K, Quarterly Report on Form 10-Q and other filings made with the U.S. Securities and Exchange Commission (SEC). Thus, actual results could be materially different. The Company undertakes no obligation to update these statements whether as a result of new information, future events or otherwise, after the date of this release, except as required by law. Pasithea Therapeutics Contact Patrick GaynesCorporate Communicationspgaynes@pasithea.com