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

Zhang, Yuanjin; Wang, Liping; Fu, Yu; Song, Hongsong; Zhao, Haiyan; Deng, Min; Zhang, Jun; Fan, Dongsheng

doi:10.3109/17482960802588059

Cited by 43 publications

(20 citation statements)

References 5 publications

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“…In our study, we could not detect any significant difference in the CSF between ALS patients and control subjects, nor was there any correlation with either disease progression or prognosis. Although elevated G‐CSF and GM‐CSF in the CSF were noted in several studies (Mitchell et al., 2009; Tateishi et al., 2010), their predictive and therapeutic values in ALS were also preliminarily evaluated (Su et al., 2013; Zhang et al., 2009). Differences in race or patient selection among the studies may be cause of these discrepancies.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the levels of CSF and serum factors in ALS

et al. 2017

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ObjectivesThe aim of this study was to identify CSF and serum factors as biomarkers that may aid in distinguishing ALS patients from control subjects and predicting ALS progression as well as prognosis.MethodsSerum and CSF samples from 105 patients with ALS and 56 control subjects were analyzed for 13 factors using ELISA. The revised ALS functional rating scale (ALSFRS‐r) was used to evaluate the overall functional status of ALS patients, and we also followed up with ALS patients either by phone or with clinic visits for five years after enrollment in this study. Finally, we examined the correlations between factor levels and various clinical parameters and evaluated the predictive value for prognosis through a multivariate statistic model.ResultsA total of eight factors were obviously elevated in CSF, and twelve markers were increased in serum. In the correlation analyses, there were trends toward higher bFGF, VEGF, MIP‐1α levels in ALS with a longer disease duration and slower disease progression in both CSF and serum. Higher MCP‐1 levels were associated with worse disease severity and faster progression, and the IFN‐γ levels were positively associated with disease progression in either CSF or serum. Finally, a better prognosis was observed with higher levels bFGF in CSF and VEGF in CSF and serum; conversely, patients with higher levels of IFN‐γ in the CSF had shorter overall survival.ConclusionsWe demonstrated that a factor profile of ALS patients is distinct from control subjects and may be useful in clinical practice and therapeutic trials.

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Section: Discussionmentioning

confidence: 99%

Evaluating the levels of CSF and serum factors in ALS

et al. 2017

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“…G-CSF has been shown to boost immune defense, attenuate inflammation, and prolong survival in ALS mice [12,19,20]. Phase I clinical trials have confirmed G-CSF-based therapy is safe for ALS treatment [42,43,44]. The G-CSF receptor CSF3R is expressed by neurons in the brain and spinal cord, where G-CSF can stimulate neural differentiation from adult neural stem cells, and it protects against apoptotic death [14,45].…”

Section: Discussionmentioning

confidence: 99%

Granulocyte Colony-Stimulating Factor Ameliorates Skeletal Muscle Dysfunction in Amyotrophic Lateral Sclerosis Mice and Improves Proliferation of SOD1-G93A Myoblasts in vitro

Rando¹,

Gasco²,

Torre³

et al. 2016

Neurodegener Dis

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Background: Amyotrophic lateral sclerosis (ALS) causes loss of upper and lower motor neurons as well as skeletal muscle (SKM) dysfunction and atrophy. SKM is one of the tissues involved in the development of ALS pathology, and studies in a SOD1-G93A mouse model of ALS have demonstrated alterations in SKM degeneration/regeneration marker expression in vivo and defective mutant myoblast proliferation in vitro. Granulocyte colony-stimulating factor (G-CSF) has been shown to alleviate SOD1-G93A pathology. However, it is unknown whether G-CSF may have a direct effect on SKM or derived myoblasts. Objective: To investigate effects of G-CSF and its analog pegfilgrastim (PEGF) on SOD1-G93A- associated SKM markers in vivo and those of G-CSF on myoblast proliferation in vitro. Methods: The effect of PEGF treatment on hematopoietic stem cell mobilization, survival, and motor function was determined. RNA expression of SKM markers associated with mutant SOD1 expression was quantified in response to PEGF treatment in vivo, and the effect of G-CSF on the proliferation of myoblasts derived from mutant and control muscles was determined in vitro. Results: Positive effects of PEGF on hematopoietic stem cell mobilization, survival, and functional assays in SOD1-G93A animals were confirmed. In vivo PEGF treatment augmented the expression of its receptor Csf3r and alleviated typical markers for mutant SOD1 muscle. Additionally, G-CSF was found to directly increase the proliferation of SOD1-G93A, but not wild-type primary myoblasts in vitro. Conclusion: Our results support the beneficial role of the G-CSF analog PEGF in a SOD1-G93A model of ALS. Thus, G-CSF andits analogs may be directly beneficial in diseases where the SKM function is compromised.

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“…The diseased animals exhibited clinical, electrophysiological, and histopathological features similar to ALS, in particular, loss of extension reflex, which is a well known motor pattern characteristic of motor neuron diseases (Kriz et al 2003;Jaworski et al 2006), and the reduction of CMAP amplitude (Liu et al 2009;Henderson et al 2009;Zhang et al 2008). Both the ultramicroscopic and the electrophysiological analysis also confirmed that 1,2 DAB neurotoxicity affects primarily the proximal segments of the motor fibers, thus resembling one of the major clinical and pathological characteristics of ALS (Williamson and Cleveland 2001;Holzbaur 2004;Cleveland and Rothstein 2001;Bruijn and Cleveland 1996).…”

Section: Discussionmentioning

confidence: 97%

Therapeutic Effect of the Combined Use of Growth Hormone Releasing Peptide-6 and Epidermal Growth Factor in an Axonopathy Model

et al. 2010

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Amyotrophic lateral sclerosis (ALS) is a disease of the central nervous system characterized by loss of spinal motor neurons, for which no effective treatment exists. Epidermal growth factor (EGF) and growth hormone releasing peptide-6 (GHRP-6) have been considered as good candidates for the treatment of this disease, due to their well documented effects in eliciting pleiotrophic and cell survival mechanisms. The aim of the present work was to evaluate the separate and combined effects of both peptides in an experimental animal model of ALS, the proximal axonopathy induced by 1,2 diacetylbenzene (1,2 DAB) in mice. The evaluations were conducted by means of behavioral tests (trapeze, tail suspension, gait pattern, and open field) and by recording the complex muscle action potential (CMAP) in three different hind limb segments: proximal S1, medial S2, and distal S3. Intraperitoneal daily administration of 1,2 DAB produced significant reduction in body weight, muscle strength, extensor reflex, spontaneous activity, and changes in gait pattern parameters. In parallel 1,2 DAB produced significant prolongation of onset latency and decrease in amplitude of CMAP and in the integrated complex action potential index. Daily administration of the separate compounds did not accelerate the recovery of the affected parameters, except for the gait pattern. The combined treatment produced significant improvement in behavioral parameters, as well as in electrophysiological recovery, particularly in the proximal segment of CMAP. The latter results confirm the proximal character of 1,2 DAB neuropathy, and suggest that combined therapy with EGF and GHRP-6 might be a good therapeutic strategy for the treatment of ALS.

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

Cited by 43 publications

References 5 publications

Evaluating the levels of CSF and serum factors in ALS

Evaluating the levels of CSF and serum factors in ALS

Granulocyte Colony-Stimulating Factor Ameliorates Skeletal Muscle Dysfunction in Amyotrophic Lateral Sclerosis Mice and Improves Proliferation of SOD1-G93A Myoblasts in vitro

Therapeutic Effect of the Combined Use of Growth Hormone Releasing Peptide-6 and Epidermal Growth Factor in an Axonopathy Model

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