title: Double-Blind, Placebo-Controlled, Randomized Phase I/IIa Study (Safety and Efficacy) with Buspirone/Levodopa/Carbidopa (SpinalonTM) in Subjects with Complete AIS A or Motor-Complete AIS B Spinal Cord Injury.
abstract: No drug treatment capable of restoring locomotor capabilities in patients suffering a motor-complete spinal cord injury (SCI) has ever been developed. We assessed the safety and efficacy of an activator of spinal locomotor neurons in humans, which were shown in paraplegic animals to elicit temporary episodes of involuntary walking.
  
  
  
  Single administration of buspirone/levodopa/carbidopa (SpinalonTM), levodopa/carbidopa (ratio 4: 1), and buspirone or placebo was performed using a dose-escalation design in 45 subjects placed in supine position who had had an SCI classified as complete (AIS A) or motor-complete/sensory incomplete (AIS B) for at least 3 months. Blood samples before and at regular intervals (15, 30, 60, 120, 240 min) after treatment were collected for hematological and pharmacokinetic (PK) analyses. Electromyographic (EMG) activity of eight muscles (four per leg) was monitored prior to and at several time points after drug administration.
  
  
  
  SpinalonTM (10-35 mg buspirone/100-350 mg levodopa/25-85 mg carbidopa) displayed no sign of safety concerns - only mild nausea was found in 3 cases. At higher doses, 50 mg/500 mg/125 mg SpinalonTM was considered to have reached maximum tolerated dose (MTD) since 3 out of 4 subjects experienced related adverse events including vomiting. PK analyses showed comparable data between groups suggesting no significant drugdrug interaction with SpinalonTM. Only the SpinalonTM-treated groups displayed significant EMG activity accompanied by locomotor-like characteristics - that is with rhythmic and bilaterally alternating bursts.
  
  
  
  Therefore, this study provides evidence of safety and preliminary efficacy following a single administration of SpinalonTM in subjects with SCI.
authors.affiliation: Research Institute of the McGill University Health Centre (MUHC), Department of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Mohan
authors.initials: M
authors.lastname: Radhakrishna
authors.affiliation: Centre Hospitalier Universitaire de Québec (CHUQ - CHUL), Neurosciences Unit, Quebec City, QC, Canada.
authors.forename: Inge
authors.initials: I
authors.lastname: Steuer
authors.affiliation: University of Montreal, Department of Surgery, Faculty of Medicine, Montreal, QC, Canada.
authors.forename: Francois
authors.initials: F
authors.lastname: Prince
authors.affiliation: University of Montreal, Department of Surgery, Faculty of Medicine, Montreal, QC, Canada.
authors.forename: Mary
authors.initials: M
authors.lastname: Roberts
authors.affiliation: University of Montreal, Department of Surgery, Faculty of Medicine, Montreal, QC, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Mongeon
authors.affiliation: Research Institute of the McGill University Health Centre (MUHC), Department of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Maryam
authors.initials: M
authors.lastname: Kia
authors.affiliation: Research Institute of the McGill University Health Centre (MUHC), Department of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Sasha
authors.initials: S
authors.lastname: Dyck
authors.affiliation: Research Institute of the McGill University Health Centre (MUHC), Department of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Matte
authors.affiliation: Nordic Life Science Pipeline Inc., Quebec City, QC, Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Vaillancourt
authors.affiliation: CHUQ-CHUL, Neurosciences Unit, RC-9800, 2705 Laurier Boulevard, Quebec City, QC, Canada, G1V 4G2, Canada.
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Guertin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002065:Buspirone / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D002230:Carbidopa / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004576:Electromyography; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013119:Spinal Cord Injuries / Q000097:blood / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D007980:Levodopa; D002230:Carbidopa; D002065:Buspirone
keywords: Electromyographic (EMG); Locomotion; drug treatment; paraplegia; spinal locomotor neurons; tetraplegia