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Use of G-CSF for the extension of the therapeutic time-window of thrombolytic stroke therapy

A technology for stroke and purpose, applied in the field of application of G-CSF for prolonging the treatment time window of thrombolytic therapy for stroke, can solve the problems of reduced efficacy, limitation and the like

Inactive Publication Date: 2012-01-11
SYGNIS BIOSCI GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, the use of rt-PA is limited by a relatively narrow time window
Recently demonstrated potency up to 4.5 hours after onset of stroke symptoms, but potency decreases rapidly over time (Hacke et al., Lancet 2004, 363:768; Hacke et al., NEngl JMed. 2008, 359:1317)

Method used

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  • Use of G-CSF for the extension of the therapeutic time-window of thrombolytic stroke therapy
  • Use of G-CSF for the extension of the therapeutic time-window of thrombolytic stroke therapy
  • Use of G-CSF for the extension of the therapeutic time-window of thrombolytic stroke therapy

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] G-CSF reduces infarct size in an embolization model

[0047] The embolism model of cerebral ischemia may represent a stroke model closer to the human situation than the filament model. To date, the efficacy of G-CSF has not been shown in embolization models. Here, an embolic stroke model was established by injecting a preformed blood clot into the rat internal carotid artery.

[0048] Male Wistar rats (n=20) weighing approximately 320 g were anesthetized with isoflurane (5% for induction, 2% for surgery, 1.2% for maintenance). A PE-50 polyethylene tube was inserted into the femoral artery for monitoring mean arterial blood pressure (MABP) and obtaining measured blood gases (pH, PaO 2 , PaCO 2 ), electrolyte (Na + , K + , Ca 2+ ) and blood glucose samples. Body temperature was continuously monitored with a rectal probe and maintained at 37.0+ / 0.3°C with a thermostatically controlled heating lamp. For embolic stroke (ES), a red blood clot (diameter = 0.35 mm , le...

Embodiment 2

[0053] G-CSF arrests the development of DWI lesions in the presence of persistent perfusion deficit

[0054] Durable filament occlusion of the MCA (suture occlusion of the right midbrain (sMCAO; Bouley et al., Neurosci Lett. 2007, 412:185)) was performed using a 4-0 silicone-coated nylon filament suture as previously described. Wistar rats (n=15) weighing approximately 320+ / 19 g were anesthetized with isoflurane (5% for induction, 2% for surgery, 1.2% for maintenance) in ambient air. A PE-50 polyethylene tube was inserted into the femoral artery for monitoring mean arterial blood pressure (MABP) and Obtain measured blood gas (pH, PaO 2 , PaCO 2 ), electrolyte (Na + , K + , Ca 2+ ) and blood glucose samples. Body temperature was continuously monitored with a rectal probe and maintained at 37.0 + / - 0.3°C with thermostatically controlled heating lamps.

[0055] Perfusion deficit and DWI damage were monitored by MRI measurements over a period of 180 min. These MRI experime...

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PUM

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Abstract

The present invention relates to the use of G-CSF and derivatives thereof for extending the therapeutic window of subsequent thrombolytic treatment of acute stroke, and thereby, allowing the diagnostic examinations which are necessary prior to the thrombolytic treatment in order to avoid hemorrhagic and other severe adverse side effects of the thrombolysis.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to USSN 61 / 153,079, filed February 17, 2006, which is hereby incorporated in its entirety. field of invention [0003] The present invention relates to the use of granulocyte colony-stimulating factor (G-CSF) polypeptide in preventing neuronal cell death in the penumbra of infarction after acute stroke. More particularly, the present invention provides methods of increasing the therapeutic window of thrombolytic therapy after acute stroke by administering a G-CSF polypeptide first, followed by thrombolytic therapy. Background of the invention [0004] Granulocyte colony stimulating factor (G-CSF) was originally identified as a hematopoietic factor in the myeloid lineage responsible for neutrophil production. Recently, the presence and activity of this factor in the central nervous system was identified. G-CSF and its receptors are upregulated after cerebral ischemia, G-CSF acts as ant...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/19
CPCA61K38/193A61P7/02A61P9/00A61P9/10A61P25/00A61P43/00
Inventor 马克·菲舍尔阿尔明·施奈德
Owner SYGNIS BIOSCI GMBH
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