Next-generation strategies to improve safety and efficacy of adeno-associated virus-based gene therapy for hemophilia: lessons from clinical trials in other gene therapies
Haematologica. 2024 Mar 7. doi: 10.3324/haematol.2023.284622. Online ahead of print.ABSTRACTThree major directions for the global progress of adeno-associated virus (AAV) vectors for gene therapies (GT) are analyzed: a) engineering vectors to increase transgene expression; b) aligning interests of the health system with costs and challenges for pharmaceutical industry; c) refining patient eligibility criteria, and endpoints definition. Currently employed AAV vectors may cause toxicity and adverse events. Furthermore, studies in animals do not fully predict risks and clinical benefits of AAV-based GT, and animal models refl...
Source: Haematologica - March 7, 2024 Category: Hematology Authors: Giovanni Di Minno Wolfgang Miesbach Giancarlo Castaman Flora Peyvandi Source Type: research
Next-generation strategies to improve safety and efficacy of adeno-associated virus-based gene therapy for hemophilia: lessons from clinical trials in other gene therapies
Haematologica. 2024 Mar 7. doi: 10.3324/haematol.2023.284622. Online ahead of print.ABSTRACTThree major directions for the global progress of adeno-associated virus (AAV) vectors for gene therapies (GT) are analyzed: a) engineering vectors to increase transgene expression; b) aligning interests of the health system with costs and challenges for pharmaceutical industry; c) refining patient eligibility criteria, and endpoints definition. Currently employed AAV vectors may cause toxicity and adverse events. Furthermore, studies in animals do not fully predict risks and clinical benefits of AAV-based GT, and animal models refl...
Source: Haematologica - March 7, 2024 Category: Hematology Authors: Giovanni Di Minno Wolfgang Miesbach Giancarlo Castaman Flora Peyvandi Source Type: research
Next-generation strategies to improve safety and efficacy of adeno-associated virus-based gene therapy for hemophilia: lessons from clinical trials in other gene therapies
Haematologica. 2024 Mar 7. doi: 10.3324/haematol.2023.284622. Online ahead of print.ABSTRACTThree major directions for the global progress of adeno-associated virus (AAV) vectors for gene therapies (GT) are analyzed: a) engineering vectors to increase transgene expression; b) aligning interests of the health system with costs and challenges for pharmaceutical industry; c) refining patient eligibility criteria, and endpoints definition. Currently employed AAV vectors may cause toxicity and adverse events. Furthermore, studies in animals do not fully predict risks and clinical benefits of AAV-based GT, and animal models refl...
Source: Haematologica - March 7, 2024 Category: Hematology Authors: Giovanni Di Minno Wolfgang Miesbach Giancarlo Castaman Flora Peyvandi Source Type: research
Next-generation strategies to improve safety and efficacy of adeno-associated virus-based gene therapy for hemophilia: lessons from clinical trials in other gene therapies
Haematologica. 2024 Mar 7. doi: 10.3324/haematol.2023.284622. Online ahead of print.ABSTRACTThree major directions for the global progress of adeno-associated virus (AAV) vectors for gene therapies (GT) are analyzed: a) engineering vectors to increase transgene expression; b) aligning interests of the health system with costs and challenges for pharmaceutical industry; c) refining patient eligibility criteria, and endpoints definition. Currently employed AAV vectors may cause toxicity and adverse events. Furthermore, studies in animals do not fully predict risks and clinical benefits of AAV-based GT, and animal models refl...
Source: Haematologica - March 7, 2024 Category: Hematology Authors: Giovanni Di Minno Wolfgang Miesbach Giancarlo Castaman Flora Peyvandi Source Type: research
Next-generation strategies to improve safety and efficacy of adeno-associated virus-based gene therapy for hemophilia: lessons from clinical trials in other gene therapies
Haematologica. 2024 Mar 7. doi: 10.3324/haematol.2023.284622. Online ahead of print.ABSTRACTThree major directions for the global progress of adeno-associated virus (AAV) vectors for gene therapies (GT) are analyzed: a) engineering vectors to increase transgene expression; b) aligning interests of the health system with costs and challenges for pharmaceutical industry; c) refining patient eligibility criteria, and endpoints definition. Currently employed AAV vectors may cause toxicity and adverse events. Furthermore, studies in animals do not fully predict risks and clinical benefits of AAV-based GT, and animal models refl...
Source: Haematologica - March 7, 2024 Category: Hematology Authors: Giovanni Di Minno Wolfgang Miesbach Giancarlo Castaman Flora Peyvandi Source Type: research
An observational study of haemophilia A patients without inhibitors using the French national claims (SNDS) database
CONCLUSION: This study provides real-world insights that advance the understanding of treatment patterns and events of interest in patients with haemophilia A on prophylactic regimens in France.PMID:38445826 | DOI:10.1080/16078454.2024.2320610 (Source: Hematology)
Source: Hematology - March 6, 2024 Category: Hematology Authors: Marc Trossa ërt Aletta Falk Laur ène Gautier Nana Kragh Olivia Van Hinloopen Remi Varin Source Type: research
The self-reactive FVIII T cell repertoire in healthy individuals relies on a short set of epitopes and public clonotypes
In this study, we conducted a comprehensive analysis of the FVIII CD4 T cell repertoire in 29 healthy donors. Sequencing of the CDR3β TCR region from isolated FVIII-specific CD4 T cells revealed a limited usage and pairing of TRBV and TRBJ genes as well as a mostly hydrophobic composition of the CDR3β region according to their auto-reactivity. The FVIII repertoire is dominated by a few clonotypes, with only 13 clonotypes accounting for half of the FVIII response. Through a large-scale epitope mapping of the full-length FVIII sequence, we identified 18 immunodominant epitopes located in the A1, A3, C1, and C2 domains and ...
Source: Frontiers in Immunology - March 6, 2024 Category: Allergy & Immunology Source Type: research
Acquired hemophilia A: a single-center study of 165 patients
CONCLUSION: Immunosuppressive therapies yield remarkably high response rates, with a CR rate exceeding 80%; notably, the regimen containing rituximab exhibits a CR rate of approximately 90%. FVIII inhibitor titer of ≥5 BU/mL and BS of ≥6 were poor predictors of CR in patients with AHA.PMID:38433975 | PMC:PMC10907205 | DOI:10.1016/j.rpth.2024.102318 (Source: Cell Research)
Source: Cell Research - March 4, 2024 Category: Cytology Authors: Dandan Yu Feng Xue Xiaofan Liu Yunfei Chen Rongfeng Fu Ting Sun Xinyue Dai Mankai Ju Huan Dong Renchi Yang Wei Liu Lei Zhang Source Type: research
Acquired hemophilia A: a single-center study of 165 patients
CONCLUSION: Immunosuppressive therapies yield remarkably high response rates, with a CR rate exceeding 80%; notably, the regimen containing rituximab exhibits a CR rate of approximately 90%. FVIII inhibitor titer of ≥5 BU/mL and BS of ≥6 were poor predictors of CR in patients with AHA.PMID:38433975 | PMC:PMC10907205 | DOI:10.1016/j.rpth.2024.102318 (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - March 4, 2024 Category: Hematology Authors: Dandan Yu Feng Xue Xiaofan Liu Yunfei Chen Rongfeng Fu Ting Sun Xinyue Dai Mankai Ju Huan Dong Renchi Yang Wei Liu Lei Zhang Source Type: research
Acquired hemophilia A: a single-center study of 165 patients
CONCLUSION: Immunosuppressive therapies yield remarkably high response rates, with a CR rate exceeding 80%; notably, the regimen containing rituximab exhibits a CR rate of approximately 90%. FVIII inhibitor titer of ≥5 BU/mL and BS of ≥6 were poor predictors of CR in patients with AHA.PMID:38433975 | PMC:PMC10907205 | DOI:10.1016/j.rpth.2024.102318 (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - March 4, 2024 Category: Hematology Authors: Dandan Yu Feng Xue Xiaofan Liu Yunfei Chen Rongfeng Fu Ting Sun Xinyue Dai Mankai Ju Huan Dong Renchi Yang Wei Liu Lei Zhang Source Type: research
Clot formation and fibrinolysis assays reveal functional differences among hemostatic agents in hemophilia A plasma
CONCLUSION: Clotting and fibrinolysis assays reveal hemostatic effects of replacement and bypassing therapies at clinically relevant concentrations. These assays may help characterize hemostatic agents and optimize dosing.PMID:38426025 | PMC:PMC10901841 | DOI:10.1016/j.rpth.2024.102337 (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - March 1, 2024 Category: Hematology Authors: Lori A Holle Jacob C Pantazis Peter L Turecek Alisa S Wolberg Source Type: research
