GM-1 Ganglioside
Gangliosides are naturally occurring molecules in nerve cell membranes. They are thought to have a role in neural development, as well as cellular recognition and neuronal communication (Yu et al. 2012). Synthetic versions of these molecules, such as monosialotetrahexosylganglioside GM1 sodium salt (commonly referred to as GM-1 ganglioside), have been used in the treatment of other neurological conditions such as stroke (Candelise & Ciccone 2002) and Parkinson’s disease (Schneider 1998). Although their exact mechanism of action is unknown, it is currently thought that gangliosides prevent cellular apoptosis, elicit anti-excitotoxic activity, and help initiate neurogenesis in the central nervous system (Mocchetti 2005).
| Author Year Country Research Design PEDro Sample Size |
Methods | Outcomes |
| Geisler et al. (2001)
Geisler et al. (2001) Geisler et al. (2001) USA RCT PEDro=8 N=760 |
Population: Age range=17-69 yr; Gender: male=80%, female=20%; Level of injury: cervical-thoracic; Severity of injury: complete=63.4%, incomplete=36.6%.
Treatment: Patients were randomly assigned to receive either low dose monosialotetrahexosylganglioside (GM-1) ganglioside (Sygen®; 300 mg loading dose, followed by 100 mg/day for 56 days), high dose Sygen® (600 mg loading dose followed by 200 mg/day for 56 days), or placebo within 72 hr of injury. Treatments were administered through a gastric nasal tube. All patients initially received methylprednisolone sodium succinate (MPSS) according to National Acute Spinal Cord Injury Study (NASCIS) II guidelines for the first 24 hr before receiving Sygen® treatment. Outcome Measures: The following at 6 months: neurological recovery using the AIS and the modified Benzel Classification scale, ASIA motor function, ASIA sensory function (pinprick and light touch), bowel and bladder function, sacral sensation, anal contraction, mortality, adverse event outcomes. Chronicity: Mean time from injury to study treatment was 55.6 hr, 54 hr and 54.4 hr for Sygen® 100 mg, Sygen® 200 mg and placebo groups, respectively. |
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| Geisler et al. 1990
Geisler et al. 1991 USA RCT PEDro=9 Ninitial=37, Nfinal=34 |
Population: Age range=18-71 yr; Gender: not specified; Level of injury: cervical-thoracic; Severity of injury: complete=29%, incomplete=71%.
Treatment: Patients were randomly assigned to receive either monosialotetrahexosylganglioside (GM-1) ganglioside (GM-1 group; 100 mg/day) or placebo within 72 hr of injury. Amount of doses varied per patient. All patients received 250 mg methylprednisolone (MP) on admission followed by 125 mg MP every 6 hr for 72 hr. Outcome Measures: The following after one year: neurological recovery based on Frankel grades, ASIA motor function, adverse event outcomes, death. Chronicity: Mean time from injury to study entry was 48.2 hr and 51 hr for the GM-1 group and placebo group, respectively. |
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Discussion
After two clinical trials using GM-1 ganglioside as a treatment option for acute SCI, it is still unclear whether this drug truly elicits significant benefits. The first small scale trial (Geisler et al. 1991, 1992) reported significant motor improvement compared to a placebo group; however, when the same authors later conducted a large scale multicenter trial, no effects were seen after the study period had ended, although the administration of GM-1 ganglioside appeared to expedite the recovery process (Geisler et al. 2001a, 2001b, 2001c). One potential reason could be the delay in treatment between the two studies; patients from the second trial did not begin to receive the drug until 24 hours after the injury to accommodate the initial mandatory dose of MP (Geisler et al. 2001c). It is possible that the results varied between these two studies because GM-1 ganglioside was administered following the optimal therapeutic window in the latter clinical trial.
Currently, there are no major adverse effects that result from using GM-1 ganglioside, although sporadic cases of Guillain-Barre syndrome have been reported (Chinnock & Roberts 2005). At this time, it is impossible to reach a conclusion regarding its effectiveness on improving feeling, movement, or quality of life for those who have acquired an SCI.
Conclusion
There is level 1b evidence (from one RCT: Geisler et al. 2001a, 2001b, 2001c) that GM-1 ganglioside is not effective in promoting neurological recovery in acute SCI individuals. However, there is level 1b evidence (from one RCT: Geisler et al. 1991, 1992) that GM-1 ganglioside may be effective in promoting neurological recovery in acute SCI individuals.
