Oral administration of a tri-therapy for central pattern generator activation in paraplegic mice: proof-of-concept of efficacy.
Biotechnol J
; 5(4): 421-6, 2010 Apr.
Article
en En
| MEDLINE
| ID: mdl-20349462
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Paraplejía
/
Médula Espinal
/
Relojes Biológicos
/
Buspirona
/
Carbidopa
/
Levodopa
/
Trastornos Neurológicos de la Marcha
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Biotechnol J
Asunto de la revista:
BIOTECNOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Alemania