GM1 Ganglioside Therapy in Acute Ischemic Stroke

Scarpino, O.; Martinazzo, C.; Magi, M.; Bruno, Roberto

doi:10.1007/978-3-642-76208-6_54

Cited by 2 publications

(4 citation statements)

References 15 publications

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“…However, the difference in the improvement of the motor component of the Toronto Stroke scale was significant on Day 28 and still in favor of GM1 on day 84, as were all 10 components of the Barthel Index. In the last study (78), significant differences were found vs. placebo for both the Fritz-Werner and the Barthel Index on Day 21 which for the Barthel Index persisted for 6 months. Overall, all 4 studies demonstrated benefits through GM1 vs. placebo in neurological outcomes.…”

Section: Therapeutic Potential In Neurological Indicationsmentioning

confidence: 91%

“…By far the greatest clinical experience with GM1 exists in the treatment of stroke with overall 14 double-blind, randomized, placebo-controlled, clinical trials in overall >2,000 patients (Table 1). The 4 largest trials enrolled 792, 502, 287, and 99 patients with acute ischemic stroke within 5, 12, 48, and 48 h from its onset, respectively (75–78). In 2 trials, higher i.v.…”

Section: Therapeutic Potential In Neurological Indicationsmentioning

confidence: 99%

“…In 2 trials, higher i.v. loading doses of 300 and 200 mg were used (75, 78), otherwise GM1 was given in all studies at constant dose levels of either 40 or 100 mg and either i.v. or i.m.…”

Section: Therapeutic Potential In Neurological Indicationsmentioning

confidence: 99%

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Gangliosides: Treatment Avenues in Neurodegenerative Disease

et al. 2019

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Gangliosides are cell membrane components, most abundantly in the central nervous system (CNS) where they exert among others neuro-protective and -restorative functions. Clinical development of ganglioside replacement therapy for several neurodegenerative diseases was impeded by the BSE crisis in Europe during the 1990s. Nowadays, gangliosides are produced bovine-free and new pre-clinical and clinical data justify a reevaluation of their therapeutic potential in neurodegenerative diseases. Clinical experience is greatest with monosialo-tetrahexosyl-ganglioside (GM1) in the treatment of stroke. Fourteen randomized controlled trials (RCTs) in overall >2,000 patients revealed no difference in survival, but consistently superior neurological outcomes vs. placebo. GM1 was shown to attenuate ischemic neuronal injuries in diabetes patients by suppression of ERK1/2 phosphorylation and reduction of stress to the endoplasmic reticulum. There is level-I evidence from 5 RCTs of a significantly faster recovery with GM1 vs. placebo in patients with acute and chronic spinal cord injury (SCI), disturbance of consciousness after subarachnoid hemorrhage, or craniocerebral injuries due to closed head trauma. In Parkinson's disease (PD), two RCTs provided evidence of GM1 to be superior to placebo in improving motor symptoms and long-term to result in a slower than expected symptom progression, suggesting disease-modifying potential. In Alzheimer's disease (AD), the role of gangliosides has been controversial, with some studies suggesting a “seeding” role for GM1 in amyloid β polymerization into toxic forms, and others more recently suggesting a rather protective role in vivo . In Huntington's disease (HD), no clinical trials have been conducted yet. However, low GM1 levels observed in HD cells were shown to increase cell susceptibility to apoptosis. Accordingly, treatment with GM1 increased survival of HD cells in vitro and consistently ameliorated pathological phenotypes in several murine HD models, with effects seen at molecular, cellular, and behavioral level. Given that in none of the clinical trials using GM1 any clinically relevant safety issues have occurred to date, current data supports expanding GM1 clinical research, particularly to conditions with high, unmet medical need.

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Section: Therapeutic Potential In Neurological Indicationsmentioning

confidence: 91%

Section: Therapeutic Potential In Neurological Indicationsmentioning

confidence: 99%

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Gangliosides: Treatment Avenues in Neurodegenerative Disease

et al. 2019

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“…In the four main multicenter clinical trials [181][182][183][184], although there was no significant difference in the mortality rate between the groups of ischemic patients treated with GM1 and the placebo-receiving controls, the subjects treated with GM1 presented an improvement trend in neurological scores (as reviewed by Magistretti and collaborators [7]).…”

Section: Gm1 In Ischemic Damage Of Adultsmentioning

confidence: 99%

GM1 Ganglioside Is A Key Factor in Maintaining the Mammalian Neuronal Functions Avoiding Neurodegeneration

Chiricozzi

Lunghi

Biase

et al. 2020

IJMS

140

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Many species of ganglioside GM1, differing for the sialic acid and ceramide content, have been characterized and their physico-chemical properties have been studied in detail since 1963. Scientists were immediately attracted to the GM1 molecule and have carried on an ever-increasing number of studies to understand its binding properties and its neurotrophic and neuroprotective role. GM1 displays a well balanced amphiphilic behavior that allows to establish strong both hydrophobic and hydrophilic interactions. The peculiar structure of GM1 reduces the fluidity of the plasma membrane which implies a retention and enrichment of the ganglioside in specific membrane domains called lipid rafts. The dynamism of the GM1 oligosaccharide head allows it to assume different conformations and, in this way, to interact through hydrogen or ionic bonds with a wide range of membrane receptors as well as with extracellular ligands. After more than 60 years of studies, it is a milestone that GM1 is one of the main actors in determining the neuronal functions that allows humans to have an intellectual life. The progressive reduction of its biosynthesis along the lifespan is being considered as one of the causes underlying neuronal loss in aged people and severe neuronal decline in neurodegenerative diseases. In this review, we report on the main knowledge on ganglioside GM1, with an emphasis on the recent discoveries about its bioactive component.

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GM1 Ganglioside Therapy in Acute Ischemic Stroke

Cited by 2 publications

References 15 publications

Gangliosides: Treatment Avenues in Neurodegenerative Disease

Gangliosides: Treatment Avenues in Neurodegenerative Disease

GM1 Ganglioside Is A Key Factor in Maintaining the Mammalian Neuronal Functions Avoiding Neurodegeneration

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