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A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury.
MedLine Citation:
PMID:  21381984     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The Rho pathway has been shown to be important in the neuronal response to growth inhibitory proteins after CNS injury. BA-210 (trademarked as Cethrin®) blocks activation of Rho and has shown promise in preclinical animal studies of spinal cord injury. This is a report of a Phase I/IIa clinical study designed to test the safety, tolerability, and neurological status of patients following a single dose of BA-210 applied during surgery following acute spinal cord injury. Patients with thoracic or cervical SCI were sequentially recruited in this dose ranging, multi-centre study of 48 patients with complete ASIA A assessment. Vital signs, clinical laboratory tests, computed tomography scans , magnetic resonance imaging, and ASIA assessment were performed in the pre-study period and in follow-up periods out to one year after treatment. The treatment-emergent adverse events that were reported were typical for a population of acute spinal cord injury patients, and no serious adverse events were attributed to the drug. The pharmacokinetic analysis showed low levels of systemic exposure to the drug, and there was high inter-patient variability. Changes in ASIA motor scores from baseline were low across all dose groups in thoracic patients (1.8 ± 5.1) and larger in cervical patients (18.6 ± 19.3). The largest change in motor score was observed in the cervical patients treated with 3 mg of Cethrin where a 27.3 ± 13.3 point improvement in ASIA motor score at 12 months was observed. Approximately 6% of thoracic patients converted from ASIA A to ASIA C or D compared to 31% of cervical patients and 66% for the 3 mg cervical cohort. While the patient numbers are small, the observed motor recovery in this open-label trial suggests that BA-210 may increase neurological recovery after complete spinal cord injury. Further clinical trials in spinal cord injury with Cethrin are planned to establish evidence of efficacy.
Authors:
Michael Fehlings; Nicholas Theodore; James Harrop; Gilles Maurais; Charles Kuntz; Christopher I Shaffrey; Brian K Kwon; Jens R Chapman; Albert Yee; Allyson Tighe; Lisa McKerracher
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-8
Journal Detail:
Title:  Journal of neurotrauma     Volume:  -     ISSN:  1557-9042     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8811626     Medline TA:  J Neurotrauma     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
University of Toronto, Surgery, 399 Bathurst Street, Suite 4W-449, Toronto, Ontario, Canada, M5T 2S8, 416-603-5627, 416-603-5298; michael.fehlings@uhn.on.ca.
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