BACKGROUNDThere is a need for a simpler and accessible intervention to heal tympanic membrane perforations than myringoplasty that is todaýs golden standard. Experimental studies have identified plasminogen as a promising agent for medical treatment of chronic tympanic membrane perforation.AIMS/OBJECTIVESThis was a phase 1, prospective, randomized, placebo-controlled study with the main objective to evaluate the safety of injecting plasminogen in the vicinity of the tympanic membrane in subjects with chronic tympanic membrane perforation.MATERIAL AND METHODSAdults diagnosed with a dry chronic tympanic membrane perforation were recruited for an injection schedule with Human plasminogen 10. Adverse events, audiometry, VAS fluctuations and size of perforation, were monitored throughout the length of the study.RESULTSIt was possible to perform the injections according to schedule in all subjects. None of the subjects experienced any severe adverse events. Most common adverse event was ear pain. No signs of ototoxicity were reported.CONCLUSIONS AND SIGNIFICANCEThis pilot study suggests that plasminogen injections close to the tympanic membrane as treatment for chronic tympanic membrane injections are safe and feasible, encouraging further dose-escalating studies.

2023-11-01·Haemophilia

Plasminogen, human‐tvmh for the treatment of children and adults with plasminogen deficiency type 1

Article

作者: Thibaudeau, Karen ; Sandset, Per Morten ; Crea, Roberto ; Shapiro, Amy D ; Nakar, Charles ; Parker, Joseph M

AbstractAimAn open‐label phase 2/3 study of plasminogen, human‐tvmh administered intravenously in paediatric and adult subjects with type 1 plasminogen deficiency was conducted. Interim data was previously reported. The final data on 15 subjects who completed the study up to a maximum of 124 weeks are reported here.MethodsThe primary objectives were to evaluate efficacy of plasminogen replacement therapy on clinically evident or visible lesions during 48 weeks of dosing and to achieve an increase in trough plasminogen activity levels by at least an absolute 10% above baseline during 12 weeks of treatment.ResultsThe primary efficacy endpoint was achieved, as 100% of subjects (n = 11) with visible and assessable non‐visible lesions at baseline demonstrated ≥ 50% improvement after 48 weeks of study drug treatment with plasminogen, human‐tvmh. All subjects achieved the targeted ≥ 10% increase in trough plasminogen activity above baseline through Week 12. Plasminogen, human‐tvmh at a dose of 6.6 mg/kg administered every 2–5 days for 48 weeks and every 1–7 days for up to 124 weeks was well tolerated.ConclusionThis study provides additional evidence regarding the long‐term safety and clinical utility of replacement therapy with human plasminogen for the treatment of children and adults with type 1 plasminogen deficiency. Plasminogen, human‐tvmh received marketing approval on June 4, 2021. This trial was registered at www.clinicaltrials.gov as #NCT02690714.

2008-03-01·Arthritis & Rheumatism

Protective effects of plasmin(ogen) in a mouse model of Staphylococcus aureus–induced arthritis

Article

作者: Yongzhi Guo ; Elin Hagström ; Jinan Li ; Tor Ny

AbstractObjectiveTo assess the functional roles of plasmin in a murine model of Staphylococcus aureus–induced bacterial arthritis.MethodsBacterial arthritis was induced in plasminogen‐deficient (Plg−/−) and wild‐type (Plg+/+) littermates by local injection of 1 × 106 colony‐forming units of S aureus into the knee joints. Human plasminogen was administered to Plg−/− mice on days 0–7 or days 7–14. Antibiotic treatment was administered to Plg−/− mice on days 7–14. Bacteria counts and histologic, immunohistochemical, and Western blot analyses were performed.ResultsIn Plg+/+ mice, S aureus counts had declined within 2 days, and by day 28 the bacteria had been completely eliminated. However, S aureus was still detectable in all injected joints from Plg−/− mice, and bacteria counts were 27 times higher than the amount injected on day 0. The extent of macrophage and neutrophil recruitment to the infected joints was comparable for Plg+/+ and Plg−/− mice on days 1, 7, and 14. The activation of these inflammatory cells appeared to be impaired in Plg−/− mice, however. Treatment of Plg−/− mice with antibiotic (cloxacillin) resulted in successful killing of the bacteria, but the necrotic tissue remained in the infected joints. When human plasminogen was given intravenously to Plg−/− mice daily for 7 days, bacterial clearance was greatly improved as compared with their untreated counterparts, and the amount of necrotic tissue in the joint cavity was dramatically reduced. The expression of interleukin 6 (IL‐6) and IL‐10 was higher in Plg+/+ mice than in Plg−/− mice during bacterial arthritis.ConclusionOur findings indicate that plasmin plays a pluripotent role in protecting against S aureus–induced arthritis by activating inflammatory cells, killing bacteria, removing necrotic tissue, and enhancing cytokine expression.

100 项与人纤溶酶原（卫光生物) 相关的药物交易

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