Gangliosides: Treatment Avenues in Neurodegenerative Disease

Détails

Ressource 1Télécharger: fneur-10-00859.pdf (2075.32 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_9492AB544725
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Gangliosides: Treatment Avenues in Neurodegenerative Disease
Périodique
Frontiers in neurology
Auteur(s)
Magistretti Pierre J., Geisler Fred H., Schneider Jay S., Li P. Andy, Fiumelli Hubert, Sipione Simonetta
ISSN
1664-2295 (Print)
ISSN-L
1664-2295
Statut éditorial
Publié
Date de publication
06/08/2019
Peer-reviewed
Oui
Volume
10
Langue
anglais
Notes
Publication types: Journal Article ; Review
Publication Status: epublish
Résumé
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.
Mots-clé
Neurology, Clinical Neurology, Alzheimer, GM1, Huntington, Parkinson, glia, neuroprotection, spinal cord injury, stroke
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/08/2019 11:03
Dernière modification de la notice
16/02/2021 7:27
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