Colony stimulating factors (including erythropoietin, granulocyte colony stimulating factor and analogues) for stroke

Bath, Philip M.W.; Sprigg, Nikola

doi:10.1002/14651858.cd005207.pub2

Cited by 16 publications

(15 citation statements)

References 21 publications

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“…It has been suggested that a specific neuronal receptor may be responsible for the neuroprotective action of EPO that consists of a heterodimer of the EPO receptor and the GM-CSF b-receptor (Brines et al, 2004), suggesting a possible inherent connection of the neuroprotective properties of both proteins. Recently, we have uncovered the neuroprotective potential of G-CSF (Meuer et al, 2006;Schabitz et al, 2003;Schneider et al, 2005Schneider et al, , 2006Schabitz and Schneider, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Hematopoietic growth factors are attractive drug candidates for stroke treatment, mostly because of their long history of safe use in humans, and their multimodal acitivities as neurotrophic factors (Rogalewski et al, 2006). Indeed, multiple clinical studies in stroke patients are ongoing for both EPO and G-CSF (Bath and Sprigg, 2006;Schabitz and Schneider, 2006). It is highly probable that GM-CSF plays a similar role in the human brain as in the rodent system: the GM-CSF receptor is expressed in the human brain in a similar pattern to the rodent, GM-CSF has antiapoptotic activity on human neuroblastoma cells, and, finally, GM-CSF appears induced by stroke intrathecally in human patients (Tarkowski et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…Both are growth factors that have been initially characterized in the hematopoietic system, but have a second prominent role in the CNS. Both factors also are among the best-studied drug candidates for stroke, and both have entered clinical development (Bath and Sprigg, 2006;Schabitz and Schneider, 2006). A number of smaller studies have already been published (for review see Bath and Sprigg, 2006), and larger studies are awaited.…”

mentioning

confidence: 99%

“…Both factors also are among the best-studied drug candidates for stroke, and both have entered clinical development (Bath and Sprigg, 2006;Schabitz and Schneider, 2006). A number of smaller studies have already been published (for review see Bath and Sprigg, 2006), and larger studies are awaited. A unique advantage of these factors is indeed their excellent tolerability and safety, together with a large body of pharmacological knowledge that has accumulated from their traditional applications (e.g., anemia or neutropenia treatment).…”

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confidence: 99%

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A Neuroprotective Function for the Hematopoietic Protein Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)

Schäbitz

Krüger

Pitzer

et al. 2007

J Cereb Blood Flow Metab

160

161

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Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine responsible for the proliferation, differentiation, and maturation of cells of the myeloid lineage, which was cloned more than 20 years ago. Here we uncovered a novel function of GM-CSF in the central nervous system (CNS). We identified the GM-CSF a-receptor as an upregulated gene in a screen for ischemia-induced genes in the cortex. This receptor is broadly expressed on neurons throughout the brain together with its ligand and induced by ischemic insults. In primary cortical neurons and human neuroblastoma cells, GM-CSF counteracts programmed cell death and induces BCL-2 and BCL-Xl expression in a dose-and time-dependent manner. Of the signaling pathways studied, GM-CSF most prominently induced the PI3K-Akt pathway, and inhibition of Akt strongly decreased antiapoptotic activity. Intravenously given GM-CSF passes the blood-brain barrier, and decreases infarct damage in two different experimental stroke models (middle cerebral artery occlusion (MCAO), and combined common carotid/distal MCA occlusion) concomitant with induction of BCL-Xl expression. Thus, GM-CSF acts as a neuroprotective protein in the CNS. This finding is remarkably reminiscent of the recently discovered functionality of two other hematopoietic factors, erythropoietin and granulocyte colony-stimulating factor in the CNS. The identification of a third hematopoietic factor acting as a neurotrophic factor in the CNS suggests a common principle in the functional evolution of these factors. Clinically, GM-CSF now broadens the repertoire of hematopoietic factors available as novel drug candidates for stroke and neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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A Neuroprotective Function for the Hematopoietic Protein Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)

Schäbitz

Krüger

Pitzer

et al. 2007

J Cereb Blood Flow Metab

160

161

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“…112 Based on these promising preclinical studies, a number of clinical studies were initiated to test the efficacy of G-CSF in stroke patients. 113 We conducted a multicenter, randomized, double-blind, placebo-controlled, dose-escalating phase IIa trial (AXIS), which was recently completed. 114 In this trial, which included 45 patients who had suffered an acute stroke, G-CSF was shown to be safe and well-tolerated.…”

Section: G-csfmentioning

confidence: 99%

Multifunctional Actions of Approved and Candidate Stroke Drugs

Minnerup

Schäbitz

2009

Neurotherapeutics

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Summary: Ischemic stroke causes brain damage by multiple pathways. Previous stroke trials have demonstrated that drugs targeting one or only a few of these pathways fail to improve clinical outcome after stroke. Drugs with multimodal actions have been suggested to overcome this challenge. In this review, we describe the mechanisms of action of agents approved for secondary prevention of ischemic stroke, such as antiplatelet, antihypertensive, and lipid-lowering drugs. These drugs exhibit considerable properties beyond their classical mechanisms, including neuroprotective and neuroregenerative properties. In addition, candidate stroke drugs currently studied in clinical phase III trials are described. Among these, albumin, hematopoietic growth factors, and citicoline have been identified as promising agents with multiple mechanisms. These drugs offer hope that additional treatment options for the acute phase after a stroke will become available in the near future.

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