Preliminary investigation of effect of granulocyte colony stimulating factor on amyotrophic lateral sclerosis

Zhang, Yuanjin; Wang, Liping; Fu, Y.; Song, Hongsong; Zhao, Hang; Deng, Min; Zhang, Jun

doi:10.1080/17482960802588059

Cited by 10 publications

(8 citation statements)

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“…This is certainly an argument for the use of G-CSF as a pharmacological agent that adresses an endogenously pre-specified mechanism. Indeed, G-CSF is currently under clinical investigation in ischemic stroke [19,20], and ALS [21-23]. …”

Section: Discussionmentioning

confidence: 99%

G-CSF protects motoneurons against axotomy-induced apoptotic death in neonatal mice

et al. 2010

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BackgroundGranulocyte colony stimulating factor (G-CSF) is a growth factor essential for generation of neutrophilic granulocytes. Apart from this hematopoietic function, we have recently uncovered potent neuroprotective and regenerative properties of G-CSF in the central nervous system (CNS). The G-CSF receptor and G-CSF itself are expressed in α motoneurons, G-CSF protects motoneurons, and improves outcome in the SOD1(G93A) transgenic mouse model for amyotrophic lateral sclerosis (ALS). In vitro, G-CSF acts anti-apoptotically on motoneuronal cells. Due to the pleiotrophic effects of G-CSF and the complexity of the SOD1 transgenic ALS models it was however not possible to clearly distinguish between directly mediated anti-apoptotic and indirectly protective effects on motoneurons. Here we studied whether G-CSF is able to protect motoneurons from purely apoptotic cell death induced by a monocausal paradigm, neonatal sciatic nerve axotomy.ResultsWe performed sciatic nerve axotomy in neonatal mice overexpressing G-CSF in the CNS and found that G-CSF transgenic mice displayed significantly higher numbers of surviving lumbar motoneurons 4 days following axotomy than their littermate controls. Also, surviving motoneurons in G-CSF overexpressing animals were larger, suggesting additional trophic effects of this growth factor.ConclusionsIn this model of pure apoptotic cell death the protective effects of G-CSF indicate direct actions of G-CSF on motoneurons in vivo. This shows that G-CSF exerts potent anti-apoptotic activities towards motoneurons in vivo and suggests that the protection offered by G-CSF in ALS mouse models is due to its direct neuroprotective activity.

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Section: Discussionmentioning

confidence: 99%

G-CSF protects motoneurons against axotomy-induced apoptotic death in neonatal mice

et al. 2010

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“…Nevertheless, in one trial, an interesting trend for slowing down disease progression was reported (Nefussy et al, 2009). Similarly, Zhang et al (2008) report on a delay in motor decline. Another clinical trial used G-CSF indirectly by treating ALS patients with an autologous transplantation of hematopoietic stem cells into the cerebrospinal fluid.…”

Section: Granulocyte-colony Stimulating Factormentioning

confidence: 83%

“…Up to now, three clinical pilot studies were conducted with G-CSF in ALS patients showing that subcutaneous G-CSF treatment is reasonably tolerated in the doses given (Cashman et al, 2008; Zhang et al, 2008; Nefussy et al, 2009). Effects of G-CSF on disease progression can not be deduced from these studies since the size of patient cohorts was too small.…”

Section: Granulocyte-colony Stimulating Factormentioning

confidence: 99%

Neurotrophic growth factors for the treatment of amyotrophic lateral sclerosis: where do we stand ?

2010

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Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that results in progressive loss of motoneurons, motor weakness and death within 3–5 years after disease onset. Therapeutic options remain limited despite substantial number of approaches that have been tested clinically. Many neurotrophic growth factors are known to promote the survival of neurons and foster regeneration in the central nervous system. Various neurotrophic factors have been investigated pre-clinically and clinically for the treatment of ALS. Although pre-clinical data appeared promising, no neurotrophic factors succeeded yet in a clinical phase III trial. In this review we discuss the rationale behind those factors, possible reasons for clinical failures, and argue for a renewal of hope in this powerful class of drugs for the treatment of ALS.

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“…In the SOD mouse model, survival was prolonged [5•]. A small pilot study in ALS patients showed that change in ALSFRS was signifi cantly less in the 3 months after treatment than in the 3 months before treatment [43]. Effi cacy is expected to be measured in a placebo-controlled, double-blind, phase 2 trial that is currently under way.…”

Section: Recombinant Human Granulocyte Colony-stimulating Factormentioning

confidence: 99%

Amyotrophic lateral sclerosis: Clinical management and research update

Andrews

2008

Curr Neurol Neurosci Rep

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that selectively affects the motor neurons of the brain and spinal cord. ALS occurs in about 1 in 100,000 individuals. Although recent advances have been made in understanding the pathogenesis of ALS, there has been no new effective pharmacotherapy since the approval of riluzole more than 10 years ago. The mainstay of clinical management includes pharmacologic management of symptoms, management of dysphagia and respiratory symptoms, palliative care, and multidisciplinary care clinics. In this review, we discuss the clinical management of ALS, recent modifications to the diagnostic criteria, and current clinical trials.

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Preliminary investigation of effect of granulocyte colony stimulating factor on amyotrophic lateral sclerosis

Cited by 10 publications

References 0 publications

G-CSF protects motoneurons against axotomy-induced apoptotic death in neonatal mice

G-CSF protects motoneurons against axotomy-induced apoptotic death in neonatal mice

Neurotrophic growth factors for the treatment of amyotrophic lateral sclerosis: where do we stand ?

Amyotrophic lateral sclerosis: Clinical management and research update

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