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Oral administration of a tri‐therapy for central pattern generator activation in paraplegic mice: Proof‐of‐concept of efficacy
Author(s) -
Guertin Pierre A.,
Ung RothVisal,
Rouleau Pascal
Publication year - 2010
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.200900278
Subject(s) - central pattern generator , medicine , hindlimb , spinal cord injury , spinal cord , levodopa , carbidopa , pharmacology , neuroscience , anesthesia , psychology , parkinson's disease , disease , psychiatry , rhythm
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.