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Biotechnol J. 2010 Apr;5(4):421-6. doi: 10.1002/biot.200900278.

Oral administration of a tri-therapy for central pattern generator activation in paraplegic mice: proof-of-concept of efficacy.

Author information

1
Laval University Medical Centre (CHUQ/CHUL), Quebec City, Canada. Pierre.Guertin@crchul.ulaval.ca

Abstract

Spinal cord injury (SCI) is a neurological condition, for which no cure exists, typically leading to an immediate and irreversible loss of sensory and voluntary motor functions accompanied by significant health problems. We conducted proof-of-concept experiments aimed at assessing efficacy upon oral administration of a novel combination therapy for central pattern generator (CPG) activation and corresponding locomotor movement generation in completely paraplegic animals. Co-administration orally (by gavage) of buspirone, levodopa and carbidopa was found to dose-dependently induce episodes of steady weight-bearing stepping in low-thoracic (Th9/10) spinal cord-transected (Tx) mice (with no other form of assistance or training). Robust hindlimb stepping with weight-bearing capabilities was induced with the tri-therapy but not with clinically relevant doses of these compounds administered separately. These results provide evidence suggesting that this drug combination may be ideally suited to constitute a first-in-class therapy (CPG activator) for locomotor activity induction in chronic SCI individuals, given that efficacy was shown using commercially available brain-permeable small molecules, already known as safe for the treatment of various neurological indications.

PMID:
20349462
DOI:
10.1002/biot.200900278
[Indexed for MEDLINE]

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