Lysophosphatidic acid receptor 1 inhibition: a potential treatment target for pulmonary fibrosis.

Autor:	Volkmann ER; Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA., Denton CP; Department of Medicine, University College London, London, UK., Kolb M; Department of Medicine, McMaster University, Hamilton, ON, Canada., Wijsenbeek-Lourens MS; Erasmus University Medical Center, Rotterdam, The Netherlands., Emson C; Translational Medicine, Horizon Therapeutics (now Amgen, Inc.), Rockville, MD, USA., Hudson K; Clinical Development, Horizon Therapeutics (now Amgen, Inc.), Deerfield, IL, USA., Amatucci AJ; Global Medical Affairs, Horizon Therapeutics (now Amgen, Inc), Deerfield, IL, USA., Distler O; Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Allanore Y; Rheumatology Department, Cochin Hospital APHP, INSERM U1016, Université Paris Cité, Paris, France., Khanna D; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA khannad@med.umich.edu.
Jazyk:	angličtina
Zdroj:	European respiratory review : an official journal of the European Respiratory Society [Eur Respir Rev] 2024 Jun 12; Vol. 33 (172). Date of Electronic Publication: 2024 Jun 12 (Print Publication: 2024).
DOI:	10.1183/16000617.0015-2024
Abstrakt:	Lysophosphatidic acid (LPA)-mediated activation of LPA receptor 1 (LPAR1) contributes to the pathophysiology of fibrotic diseases such as idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc). These diseases are associated with high morbidity and mortality despite current treatment options. The LPA-producing enzyme autotaxin (ATX) and LPAR1 activation contribute to inflammation and mechanisms underlying fibrosis in preclinical fibrotic models. Additionally, elevated levels of LPA have been detected in bronchoalveolar lavage fluid from patients with IPF and in serum from patients with SSc. Thus, ATX and LPAR1 have gained considerable interest as pharmaceutical targets to combat fibrotic disease and inhibitors of these targets have been investigated in clinical trials for IPF and SSc. The goals of this review are to summarise the current literature on ATX and LPAR1 signalling in pulmonary fibrosis and to help differentiate the novel inhibitors in development. The mechanisms of action of ATX and LPAR1 inhibitors are described and preclinical studies and clinical trials of these agents are outlined. Because of their contribution to numerous physiologic events underlying fibrotic disease, ATX and LPAR1 inhibition presents a promising therapeutic strategy for IPF, SSc and other fibrotic diseases that may fulfil unmet needs of the current standard of care. Competing Interests: Conflict of interest: E.R. Volkmann has received consulting fees from Boehringer Ingelheim, CSL Behring, GSK and Roche; speaking fees (unbranded disease state lectures) from Boehringer Ingelheim; and grant support from Boehringer Ingelheim, Corbus, Forbius, Horizon Therapeutics (now Amgen, Inc), Kadmon and Prometheus. C.P. Denton has received research grants to his institution from Arxx Therapeutics, GSK, Horizon (now Amgen, Inc) and Servier; and consulting fees from Acceleron, Arxx Therapeutics, Bayer, Boehringer Ingelheim, CSL Behring, Galapagos, GSK, Janssen, Lilly, Roche and Sanofi. M. Kolb reports grants from Boehringer Ingelheim, the Canadian Institute for Health Research, Structure Therapeutics and United Therapeutics; and personal fees from AbbVie, Algernon, Bellerophon, Boehringer Ingelheim, Cipla, CSL Behring, DevPro Biopharma, European Respiratory Journal, Horizon (now Amgen, Inc), LabCorp, Nitto Denko, Pieris, Roche, Structure Therapeutics and United Therapeutics. M.S. Wijsenbeek-Lourens reports grants to her institution from AstraZeneca/Daiichi-Sankyo, Boehringer Ingelheim, the Dutch Lung Foundation, the Dutch Pulmonary Fibrosis Patients Association, Hoffmann-La Roche, The Netherlands Organisation for Health Research and Development, Sarcoidosis.nl and the Thorax Foundation; and consultancy fees paid to her institution from AstraZeneca, Boehringer Ingelheim, BMS, CSL Behring, Galapagos, Galecto, Hoffmann-La Roche, Horizon Therapeutics (now Amgen, Inc), Kinevant Sciences, Molecure, NeRRe, Novartis, PureTech, Thyron, Trevi and Vicore. C. Emson and K. Hudson are employees of Horizon Therapeutics (now Amgen, Inc) and own stock. A.J. Amatucci was employed at Horizon Therapeutics (now Amgen, Inc) during development of this manuscript. O. Distler has/had a consultancy relationship with and/or has received research funding from and/or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last 3 calendar years: 4P-Pharma, AbbVie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Orion, Prometheus, Redxpharma, Roivant, Topadur and UCB; has a patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143); and is co-founder of CITUS AG. Y. Allanore has received consulting fees from AbbVie, AstraZeneca, Boehringer Ingelheim, Janssen, Galderma, Medsenic and Prometheus. D. Khanna has received consulting fees from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Chemomab, CSL Behring, GSK, Merck, Novartis, Prometheus, Roche and UCB; and grant support from BMS, Boehringer Ingelheim, Horizon Therapeutics (now Amgen, Inc), Pfizer and Prometheus. (Copyright ©The authors 2024.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu