Glycosaminoglycans boost insulin-like growth factor-I-promoted neuroprotection: blockade of motor neuron death in the wobbler mouse

Vergani, Letizia; Losa, Massimo; Lesma, Elena; Giulio, Anna Maria Di; Torsello, Antonio; Müller, Eugenio E.; Gorio, Alfredo

doi:10.1016/s0306-4522(99)00095-0

Cited by 24 publications

(27 citation statements)

References 43 publications

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“…However, neither muscle activity nor the rate of motor neuron loss was modified by the treatment (Ikeda et al 1995a). The co-treatment with IGF-I and glycosaminoglycans (GAGs) markedly improved the nerve regrowth and muscle reinnervation and consequently delayed the clinical progression in wobbler mice (Gorio et al 1998; Vergani et al 1999). A similar effect was observed even with reduced dosage of IGF-I (Gorio et al 2002).…”

Section: Towards the Treatment Of Alsmentioning

confidence: 99%

The wobbler mouse, an ALS animal model

2013

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This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking similarities to ALS. The cellular effects of the wobbler mutation, cellular transport defects, neurofilament aggregation, neuronal hyperexcitability and neuroinflammation closely resemble human ALS. Now, 57 years after the first report on the wobbler mouse we summarize the progress made in understanding the disease mechanism and testing various therapeutic approaches and discuss the relevance of these advances for human ALS. The identification of the causative mutation linking the wobbler mutation to a vesicle transport factor and the research focussed on the cellular basis and the therapeutic treatment of the wobbler motor neuron degeneration has shed new light on the molecular pathology of the disease and might contribute to the understanding the complexity of ALS.

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Section: Towards the Treatment Of Alsmentioning

confidence: 99%

The wobbler mouse, an ALS animal model

2013

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“…Motor neuron tissue cultures have shown that IGF-I is effective in enhancing survival of embryonic motor neurons and reduce their susceptibility to glutamate induced neurotoxicity 1. Previous work with animal models has shown that IGF-I can delay motor neuron cell death 2,3. The results of two previous phase III clinical trials of insulin-like growth factor type I (IGF-1) in ALS were inconsistent 4,5.…”

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confidence: 99%

Subcutaneous IGF-1 is not beneficial in 2-year ALS trial

Sorenson¹,

Windbank²,

Mandrekar³

et al. 2008

Neurology

229

126

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Background Previous human clinical trials of insulin-like growth factor type I (IGF-1) in amyotrophic lateral sclerosis (ALS) have been inconsistent. This phase III, randomized, double-blind, placebo-controlled study was undertaken to address whether IGF-1 benefited patients with ALS. Methods A total of 330 patients from 20 medical centers were randomized to receive 0.05 mg/kg body weight of human recombinant IGF-1 given subcutaneously twice daily or placebo for 2 years. The primary outcome measure was change in their manual muscle testing score. Secondary outcome measures included tracheostomy-free survival and rate of change in the revised ALS functional rating scale. Intention to treat analysis was used. Results There was no difference between treatment groups in the primary or secondary outcome measures after the 2-year treatment period. Conclusions Insulin-like growth factor type I does not provide benefit for patients with amyotrophic lateral sclerosis.

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“…Grounds further hypothesizes that reduction of IGF-1 signaling may play a prominent role in motor neurons loss (Grounds, 2002). In support of this hypothesis, it has been demonstrated that IGF-1 administration has positive effects on neuronal function by preventing apoptotic death, and by stimulating axonal sprouting and repair of damaged axons (Lewis et al, 1993; Festoff et al, 1995; Vergani et al, 1999). …”

Section: Age-related Changes In Igf-1 Actionsmentioning

confidence: 86%

Modulation of GH/IGF-1 axis: Potential strategies to counteract sarcopenia in older adults

Giovannini

Marzetti

Borst

et al. 2008

Mechanisms of Ageing and Development

116

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Aging is associated with progressive decline of skeletal muscle mass and function. This condition, termed sarcopenia, is associated with several adverse outcomes, including loss of autonomy and mortality. Due to the high prevalence of sarcopenia, a deeper understanding of its pathophysiology and possible remedies represents a high public health priority. Evidence suggests the existence of a relationship between declining growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels and age-related changes in body composition and physical function. Therefore, the age-dependent decline of GH and IGF-1 serum levels may promote frailty by contributing to the loss of muscle mass and strength. Preclinical studies showed that infusion of angiotensin II produced a marked reduction in body weight, accompanied by decreased serum and muscle levels of IGF-1. Conversely, overexpression of muscle-specific isoform of IGF-1 mitigates angiotensin II-induced muscle loss. Moreover, IGF-1 serum levels have been shown to increase following angiotensin converting enzyme inhibitors (ACEIs) treatment. Here we will review the most recent evidence regarding age-related changes of the GH/IGF-1 axis and its modulation by several interventions, including ACEIs which might represent a potential novel strategy to delay the onset and impede the progression of sarcopenia.

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Glycosaminoglycans boost insulin-like growth factor-I-promoted neuroprotection: blockade of motor neuron death in the wobbler mouse

Cited by 24 publications

References 43 publications

The wobbler mouse, an ALS animal model

The wobbler mouse, an ALS animal model

Subcutaneous IGF-1 is not beneficial in 2-year ALS trial

Modulation of GH/IGF-1 axis: Potential strategies to counteract sarcopenia in older adults

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