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<https://discovery.ucl.ac.uk/id/eprint/10163189> <http://purl.org/dc/terms/title> "Modulation of systemic sclerosis pathobiology by purified human factor XIII - in vitro and in vivo studies"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10163189> <http://purl.org/ontology/bibo/abstract> "Systemic sclerosis (SSc) is a multi-system autoimmune disease with significant\r\nmorbidity, mortality and an unmet therapeutic need. The pathogenesis of SSc\r\ninvolves dysfunctional immune signalling, including thrombospondin-1 (TSP-1)\r\nsignalling, fibroblast behaviour and vascular development.\r\nFactor XIII (FXIII) is an enzyme involved in coagulation and in wound healing by\r\npromoting angiogenesis via inhibition of TSP-1. Animal research and previous\r\nsmall studies suggest that therapeutic administration of factor XIII could improve\r\nvascular function in SSc.\r\nThis thesis addresses the hypothesis that FXIII supplementation may affect the\r\npathogenesis of SSc via effects on vascular and connective tissue biology. This is\r\nexplored in two interlinked clinical trials: a single-dose open-label study assessing\r\nthe safety and pharmacokinetics of human factor XIII treatment in SSc; followed by\r\na phase II, double-blind, randomised, placebo-controlled study to investigate the\r\nsafety and efficacy of factor XIII treatment in SSc.\r\nThe main objective of the clinical trials was met by demonstrating that FXIII is safe\r\nand well tolerated in SSc. The trial did not meet its primary endpoints, but there\r\nwas a trend towards improvement in Raynaud’s phenomenon in the FXIII group.\r\nSerum from patients and controls was analysed to quantify candidate biomarkers\r\nfor SSc and the proposed mechanism of action of factor XIII. Previous work\r\nconfirming that cartilage oligomeric protein, TSP-1 and tumour necrosis factor\r\nalpha are raised in SSc serum was reproduced. TSP-1 levels fell significantly in the\r\nserum of participants who received FXIII, supporting the hypothesis that FXIII\r\nmodulates TSP-1. Further studies with different patient populations and FXIII\r\ndoses could investigate the role of this suppression further in a clinical setting.\r\nMy results support further exploration of the role of FXIII in SSc pathogenesis and\r\nsuggest that therapeutic strategies to modulate links between coagulation and\r\ntissue repair using FXIII are safe and feasible."^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10163189> <http://purl.org/dc/terms/date> "2023-01-28" .
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