Prolonged effect of a new O-glycoPEGylated FVIII (N8-GP) in a murine saphenous vein bleeding model

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Prolonged effect of a new O-glycoPEGylated FVIII (N8-GP) in a murine saphenous vein bleeding model. / Pastoft, Anne Engedahl; Ezban, M.; Tranholm, M.; Lykkesfeldt, Jens; Lauritzen, B.

In: Haemophilia Online, Vol. 19, No. 6, 2013, p. 913-919.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Pastoft, AE, Ezban, M, Tranholm, M, Lykkesfeldt, J & Lauritzen, B 2013, 'Prolonged effect of a new O-glycoPEGylated FVIII (N8-GP) in a murine saphenous vein bleeding model', Haemophilia Online, vol. 19, no. 6, pp. 913-919. https://doi.org/10.1111/hae.12198

APA

Pastoft, A. E., Ezban, M., Tranholm, M., Lykkesfeldt, J., & Lauritzen, B. (2013). Prolonged effect of a new O-glycoPEGylated FVIII (N8-GP) in a murine saphenous vein bleeding model. Haemophilia Online, 19(6), 913-919. https://doi.org/10.1111/hae.12198

Vancouver

Pastoft AE, Ezban M, Tranholm M, Lykkesfeldt J, Lauritzen B. Prolonged effect of a new O-glycoPEGylated FVIII (N8-GP) in a murine saphenous vein bleeding model. Haemophilia Online. 2013;19(6):913-919. https://doi.org/10.1111/hae.12198

Author

Pastoft, Anne Engedahl ; Ezban, M. ; Tranholm, M. ; Lykkesfeldt, Jens ; Lauritzen, B. / Prolonged effect of a new O-glycoPEGylated FVIII (N8-GP) in a murine saphenous vein bleeding model. In: Haemophilia Online. 2013 ; Vol. 19, No. 6. pp. 913-919.

Bibtex

@article{ab45eae678e44f75aea3dda2105be4fb,
title = "Prolonged effect of a new O-glycoPEGylated FVIII (N8-GP) in a murine saphenous vein bleeding model",
abstract = "Prophylaxis in severe haemophilia significantly increases health-related quality of life for patients, but the dosing frequency still constitutes a challenge. Thus, there is a need for new treatment options, utilizing compounds with longer duration of action, while still maintaining potency. The objective of this study was to evaluate the acute and prolonged effects of a new glycoPEGylated recombinant factor VIII (rFVIII) (N8-GP) in a venous bleeding model in haemophilia A mice and to compare the efficacy and potency to turoctocog alfa (rFVIII). Following intravenous administration of turoctocog alfa or N8-GP to normal and FVIII-deficient mice, bleeding time and blood loss from a saphenous vein incision were evaluated in an acute dose-response study and a duration of action study. In the acute setting, N8-GP dose dependently reduced the number and duration of bleeding episodes as well as blood loss compared to FVIII-deficient mice, reaching statistical significance at doses as low as 5-10 U kg(-1) . In the duration of action study, a significantly prolonged and maintained effect of N8-GP was found for up to 48 h after dosing, whereas the effect of rFVIII was no longer present for any end-points 24 h after dosing. Seventy-two hours after dosing, no significant effect of either compound was found. This study shows a prolonged haemostatic effect of N8-GP compared to rFVIII supporting other recent studies that N8-GP may hold a potential to increase the quality of life for patients with haemophilia A by reducing dosing frequency.",
keywords = "Faculty of Health and Medical Sciences, haemophilia A, mice, PEGylation, rFVIII, venous bleeding",
author = "Pastoft, {Anne Engedahl} and M. Ezban and M. Tranholm and Jens Lykkesfeldt and B. Lauritzen",
note = "{\circledC} 2013 John Wiley & Sons Ltd.",
year = "2013",
doi = "10.1111/hae.12198",
language = "English",
volume = "19",
pages = "913--919",
journal = "Haemophilia",
issn = "1351-8216",
publisher = "Wiley-Blackwell",
number = "6",

}

RIS

TY - JOUR

T1 - Prolonged effect of a new O-glycoPEGylated FVIII (N8-GP) in a murine saphenous vein bleeding model

AU - Pastoft, Anne Engedahl

AU - Ezban, M.

AU - Tranholm, M.

AU - Lykkesfeldt, Jens

AU - Lauritzen, B.

N1 - © 2013 John Wiley & Sons Ltd.

PY - 2013

Y1 - 2013

N2 - Prophylaxis in severe haemophilia significantly increases health-related quality of life for patients, but the dosing frequency still constitutes a challenge. Thus, there is a need for new treatment options, utilizing compounds with longer duration of action, while still maintaining potency. The objective of this study was to evaluate the acute and prolonged effects of a new glycoPEGylated recombinant factor VIII (rFVIII) (N8-GP) in a venous bleeding model in haemophilia A mice and to compare the efficacy and potency to turoctocog alfa (rFVIII). Following intravenous administration of turoctocog alfa or N8-GP to normal and FVIII-deficient mice, bleeding time and blood loss from a saphenous vein incision were evaluated in an acute dose-response study and a duration of action study. In the acute setting, N8-GP dose dependently reduced the number and duration of bleeding episodes as well as blood loss compared to FVIII-deficient mice, reaching statistical significance at doses as low as 5-10 U kg(-1) . In the duration of action study, a significantly prolonged and maintained effect of N8-GP was found for up to 48 h after dosing, whereas the effect of rFVIII was no longer present for any end-points 24 h after dosing. Seventy-two hours after dosing, no significant effect of either compound was found. This study shows a prolonged haemostatic effect of N8-GP compared to rFVIII supporting other recent studies that N8-GP may hold a potential to increase the quality of life for patients with haemophilia A by reducing dosing frequency.

AB - Prophylaxis in severe haemophilia significantly increases health-related quality of life for patients, but the dosing frequency still constitutes a challenge. Thus, there is a need for new treatment options, utilizing compounds with longer duration of action, while still maintaining potency. The objective of this study was to evaluate the acute and prolonged effects of a new glycoPEGylated recombinant factor VIII (rFVIII) (N8-GP) in a venous bleeding model in haemophilia A mice and to compare the efficacy and potency to turoctocog alfa (rFVIII). Following intravenous administration of turoctocog alfa or N8-GP to normal and FVIII-deficient mice, bleeding time and blood loss from a saphenous vein incision were evaluated in an acute dose-response study and a duration of action study. In the acute setting, N8-GP dose dependently reduced the number and duration of bleeding episodes as well as blood loss compared to FVIII-deficient mice, reaching statistical significance at doses as low as 5-10 U kg(-1) . In the duration of action study, a significantly prolonged and maintained effect of N8-GP was found for up to 48 h after dosing, whereas the effect of rFVIII was no longer present for any end-points 24 h after dosing. Seventy-two hours after dosing, no significant effect of either compound was found. This study shows a prolonged haemostatic effect of N8-GP compared to rFVIII supporting other recent studies that N8-GP may hold a potential to increase the quality of life for patients with haemophilia A by reducing dosing frequency.

KW - Faculty of Health and Medical Sciences

KW - haemophilia A

KW - mice

KW - PEGylation

KW - rFVIII

KW - venous bleeding

U2 - 10.1111/hae.12198

DO - 10.1111/hae.12198

M3 - Journal article

C2 - 23730746

VL - 19

SP - 913

EP - 919

JO - Haemophilia

JF - Haemophilia

SN - 1351-8216

IS - 6

ER -

ID: 104569930