{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:37:52Z","timestamp":1790242672271,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Beta\u2010thalassaemia is an inherited blood disorder characterised by ineffective erythropoiesis and anaemia. Consequently, hepcidin expression is reduced resulting in increased iron absorption and primary iron overload. Hepcidin is under the negative control of transmembrane serine protease 6 (TMPRSS6) via cleavage of haemojuvelin (HJV), a co\u2010receptor for the bone morphogenetic protein (BMP)\u2010mothers against decapentaplegic homologue (SMAD) signalling pathway. Considering the central role of the TMPRSS6\/HJV\/hepcidin axis in iron homeostasis, the inhibition of TMPRSS6 expression represents a promising therapeutic strategy to increase hepcidin production and ameliorate anaemia and iron overload in \u03b2\u2010thalassaemia. In the present study, we investigated a small interfering RNA (siRNA) conjugate optimised for hepatic targeting of\n                    <jats:italic>Tmprss6<\/jats:italic>\n                    (SLN124) in \u03b2\u2010thalassaemia mice (Hbb\n                    <jats:sup>th3\/+<\/jats:sup>\n                    ). Two subcutaneous injections of SLN124 (3\u00a0mg\/kg) were sufficient to normalise hepcidin expression and reduce anaemia. We also observed a significant improvement in erythroid maturation, which was associated with a significant reduction in splenomegaly. Treatment with the iron chelator, deferiprone (DFP), did not impact any of the erythroid parameters. However, the combination of SLN124 with DFP was more effective in reducing hepatic iron overload than either treatment alone. Collectively, we show that the combination therapy can ameliorate several disease symptoms associated with chronic anaemia and iron overload, and therefore represents a promising pharmacological modality for the treatment of \u03b2\u2010thalassaemia and related disorders.\n                  <\/jats:p>","DOI":"10.1111\/bjh.17428","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T06:29:58Z","timestamp":1620109798000},"page":"200-210","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["SLN124, a GalNac\u2010siRNA targeting transmembrane serine protease 6, in combination with deferiprone therapy reduces ineffective erythropoiesis and hepatic iron\u2010overload in a mouse model of 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