Current Research Studies

SC-N148, Hypoplasminogenemia: An International RetroSpecTive and PrOspective CohoRt StudY


What is the goal of the study?

Plasminogen deficiency (PLGD) is a rare genetic systemic disorder with an estimated incidence of 1-2 per million population and is due to homozygous/compound heterozygous mutations in PLG, the gene coding for plasminogen (PLG). These PLG mutations result in decreased PLG activity (Act) and antigen (Ag) levels. PLG plays a central role in fibrinolysis, wound healing, and embryogenesis. Clinical manifestations of PLGD result from inadequately lysed fibrin that lead to accumulation of woody pseudomembranes in tissues and organs that impair organ function, resulting in morbidity, decreased quality of life, and at times mortality. Diagnosis relies upon clinical presentation and PLG Act/Ag levels. Knowledge of PLGD stems from case reports and small series. Phenotypic disease expression does not correlate with PLG Act or genetic defect. No biomarkers have been identified to predict clinical course. Current therapies are inadequate. Systematic prospective data collection coupled with serial biologic samples collected from Persons with PLGD (PwPLGD) and first-degree family members has not been performed. Knowledge gaps include identification of contributing factors to and triggers of disease manifestations, inability to predict disease course, and insufficient real-world data for individualized use of new therapeutics. To address unmet needs, a retrospective and prospective data collection system of a large cohort of PwPLGD and their family members has been developed to define the natural history of PLGD. Phenotypic data combined with genetic and advanced laboratory testing will be used to investigate disease course predictors and evaluate/elucidate phenotypic relationships. A specimen biobank will serve as a resource for further analyses. The Hypoplasminogenemia: An International RetroSpecTive and PrOspective CohoRt StudY (HISTORY) addresses key knowledge gaps of PLGD natural history, and builds on the productivity/infrastructure of the established collaborative efforts of research teams at the Indiana Hemophilia and Thrombosis Center (IHTC) and the University of Milan (UMIL). To explore potential disease contributors/triggers, researchers at the University of Wollongong will study bacterial manipulation of mutant PLGs to invade and evade the immune system. Overarching study goals are to analyze phenotypic heterogeneity, identify markers to predict disease course, and develop improved methods to utilize new therapeutics.

Who can participate in the study?

Please contact the study team listed below to learn more.

Study Team: