Hemophilia gene therapy knowledge and perceptions: Results of an international survey

Background Hemophilia gene therapy is a rapidly evolving therapeutic approach in which a number of programs are approaching clinical development completion. Objective The aim of this study was to evaluate knowledge and perceptions of a variety of health care practitioners and scientists about gene therapy for hemophilia. Methods This survey study was conducted February 1 to 18, 2019. Survey participants were members of the ISTH, European Hemophilia Consortium, European Hematology Association, or European Association for Hemophilia and Allied Disorders with valid email contacts. The online survey consisted of 36 questions covering demographic information, perceptions and knowledge of gene therapy for hemophilia, and educational preferences. Survey results were summarized using descriptive statistics. Results Of the 5117 survey recipients, 201 responded from 55 countries (4% response rate). Most respondents (66%) were physicians, and 59% were physicians directly involved in the care of people with hemophilia. Among physician respondents directly involved in hemophilia care, 35% lacked the ability to explain the science of adeno-associated viral gene therapy for hemophilia, and 40% indicated limited ability or lack of comfort answering patient questions about gene therapy for hemophilia based on clinical trial results to date. Overall, 75% of survey respondents answered 10 single-answer knowledge questions correctly, 13% incorrectly, and 12% were unsure of the correct answers. Conclusions This survey highlighted knowledge gaps and educational needs related to gene therapy for hemophilia and, along with other inputs, has informed the development of "Gene Therapy in Hemophilia: An ISTH Education Initiative.

Molecular Mechanisms of Membrane Deformation by I-BAR Domain Proteins

SummaryBackgroundGeneration of membrane curvature is critical for the formation of plasma membrane protrusions and invaginations and for shaping intracellular organelles. Among the central regulators of membrane dynamics are the BAR superfamily domains, which deform membranes into tubular structures. In contrast to the relatively well characterized BAR and F-BAR domains that promote the formation of plasma membrane invaginations, I-BAR domains induce plasma membrane protrusions through a poorly understood mechanism.ResultsWe show that I-BAR domains induce strong PI(4,5)P2 clustering upon membrane binding, bend the membrane through electrostatic interactions, and remain dynamically associated with the inner leaflet of membrane tubules. Thus, I-BAR domains induce the formation of dynamic membrane protrusions to the opposite direction than do BAR and F-BAR domains. Strikingly, comparison of different I-BAR domains revealed that they deform PI(4,5)P2-rich membranes through distinct mechanisms. IRSp53 and IRTKS I-BARs bind membranes mainly through electrostatic interactions, whereas MIM and ABBA I-BARs additionally insert an amphipathic helix into the membrane bilayer, resulting in larger tubule diameter in vitro and more efficient filopodia formation in vivo. Furthermore, FRAP analysis revealed that whereas the mammalian I-BAR domains display dynamic association with filopodia, the C. elegans I-BAR domain forms relatively stable structures inside the plasma membrane protrusions.ConclusionsThese data define I-BAR domain as a functional member of the BAR domain superfamily and unravel the mechanisms by which I-BAR domains deform membranes to induce filopodia in cells. Furthermore, our work reveals unexpected divergence in the mechanisms by which evolutionarily distinct groups of I-BAR domains interact with PI(4,5)P2-rich membranes

Distribution of responsibilities for sustainability: The role of the corporatation and other actors in the economic system

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Individualised Prophylaxis with Recombinant Factor IX FC Fusion Protein (RFIXFC) in Adults/Adolescents With Haemophilia B: Updated Interim Results of the B-YOND Extension Study

Poster presentatio