{"entity": "publication", "iuid": "84d416bb19ba431ba5359f50ec9a3c86", "timestamp": "2026-08-29T04:17:12.144Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/84d416bb19ba431ba5359f50ec9a3c86.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/84d416bb19ba431ba5359f50ec9a3c86"}}, "title": "Pharmacological inhibition of MutT homolog 1 (MTH1) in allergic airway inflammation as a novel treatment strategy.", "authors": [{"family": "Adler", "given": "Anna", "initials": "A"}, {"family": "Bergwik", "given": "Jesper", "initials": "J"}, {"family": "Padra", "given": "M\u00e9dea", "initials": "M"}, {"family": "Papareddy", "given": "Praveen", "initials": "P"}, {"family": "Schmidt", "given": "Tobias", "initials": "T"}, {"family": "Dahlgren", "given": "Madelene", "initials": "M"}, {"family": "Kahn", "given": "Robin", "initials": "R"}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW"}, {"family": "Egesten", "given": "Arne", "initials": "A"}], "type": "journal article", "published": "2025-03-14", "journal": {"title": "Respir. Res.", "issn": "1465-993X", "volume": "26", "issue": "1", "pages": "101", "issn-l": "1465-9921"}, "abstract": "Despite progress in the treatment of asthma, there is an unmet need for additional therapeutic strategies, not least to avoid side-effects of corticosteroids. The enzyme MutT homolog 1 (MTH1) hydrolyzes oxidized purines and prevents their insertion to DNA. Small molecule inhibition of MTH1 has shown promising therapeutic effects in both cancer and inflammatory conditions. In this study, a small molecule inhibitor of MTH1 (TH1579), was investigated in models of allergic inflammation.\n\nIn vitro, effects on T cell proliferation and apoptosis were investigated. Furthermore, a murine model, using female BALB/c mice, of OVA-induced allergic airway inflammation was used to investigate effects from MTH1-inhibition in vivo.\n\nInhibition of MTH1 prevented T cell proliferation in vitro and induced apoptosis in isolated human CD4+ T cells. However, the viability of isolated human eosinophils was unaffected by MTH1 inhibition in vitro. Pharmacological inhibition of MTH1 in a murine model of allergic airway inflammation reduced mucus production, recruitment of inflammatory cells, such as T cells and eosinophils in the BAL fluid and lung tissue, reduced plasma levels of total IgE and OVA-specific IgE, IgG, and IgG1, as well as reduced IL-13 levels in BAL fluid, lung tissue and plasma.\n\nMTH1 inhibition reduced proliferation and promoted apoptosis of T cells in vitro. In vivo, TH1579 dampened the type 2 associated immune response in a murine model. These findings suggest that MTH1 could serve as a novel target to treat allergic airway inflammation.", "doi": "10.1186/s12931-025-03175-z", "pmid": "40087604", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11909806"}, {"db": "pii", "key": "10.1186/s12931-025-03175-z"}], "notes": [], "created": "2026-08-21T12:39:12.371Z", "modified": "2026-08-21T12:39:12.399Z"}