The Impact of combination biologics on treadmill quadrupedal locomotion after spinal cord hemi-contusion in non-human primates

Introduction.
Non-human primates can be trained to ambulate on a treadmill. Cervical contusions lead to both upper and lower extremity functional deficits. These can be analyzed in a coupled manner using kinematic tracking of forelimb and hindlimb joint cycles. We tested the following hypotheses. 1) Kinematic analysis has sufficient sensitivity to detect differences in injury severity after C3/4 hemi-contusion. 2) The impact of locally delivered experimental therapeutics including autologous Schwann cells (aSC) and lentivirus expressing chondroitinase ABC (LV-ChABC) on gait is evident on limb-coupled kinematic analysis. 3) This analysis adds relevant data not evident in hand dexterity testing.
Methods.
Five monkeys (M. fascicularis) were pre-trained. Following a right sided hemi-contusion the animals were randomized into A) No treatment controls (n= 1); B) LV-ChABC injected perilesionally 2 hours post spinal cord injury (n=2); C) LV-ChABC injection and transplant of aSC 14 days post-injury (n=2). Treadmill activity occurred weekly. Quadrupedal locomotion analysis was performed pre-injury, 3 and 6 months post-injury. Joints in the left and right sides were marked with ultraviolet ink and data was captured using black lights and a Vicon Motus tracking system. The variables assessed were joint track consistency and distance, stride length, and height.
Results.
All animals, except those receiving LV-ChABC, had notable deficits in quadrupedal locomotion at 3 months post-injury (step height, length). The wrist and ankle joint cycles were inconsistent possibly due to impaired strength, proprioception, and balance. By six months post-injury the joint cycles of groups A and B were more consistent and approached baseline. Animals in group C (aSC) showed persistent gait impairments. Analysis of contusion parameters including force delivered and ultrasound quantitative assessment of injury volume do not account for the behavioral differences.
Conclusion.
Kinematic quadrupedal locomotor assessment is useful to quantify recovery, adding to assessments of hand dexterity. The animals continue to survive. Final MRI, histology, and CST tracing will be correlated to the quadrupedal kinematic analysis.

Authors
*R. DE NEGRI1, A. J. SANTAMARIA1, F. D. BENAVIDES1, A. Y. FLORES1, N. JAMES4, Y. NUNEZ2, J. P. SOLANO2, J. VERHAAGEN5,6, E. J. BRADBURY4, J. D. GUEST1,3;
1The Miami Project to Cure Paralysis, 2Pedriatic Critical Care, 3Neurolog. Surgery, Univ. of Miami, Miller Sch. of Med., Miami, FL; 4The Wolfson Ctr. for Age-Related Dis., King’s Col. London, London, United Kingdom; 5Dept. of Mol. and Cell. Neurobio., Vrije Univ. Amsterdam, Ctr. for Neurogenomics and Cognition research, Amsterdan, Netherlands; 6Lab. for Neuroregeneration, Netherlands Inst. for Neurosci., Amsterdam, Netherlands
Disclosures
R. De Negri: None. A.J. Santamaria: None. F.D. Benavides: None. A.Y. Flores: None. N. James: None. Y. Nunez: None. J.P. Solano: None. J. Verhaagen: None. E.J. Bradbury: None. J.D. Guest: None.

LINK: Session 158 – Spinal Cord Injury and Plasticity

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One Response to The Impact of combination biologics on treadmill quadrupedal locomotion after spinal cord hemi-contusion in non-human primates

  1. Lisa Landrum says:

    Is this moving us closer to clinical trials?

    Lisa landrum

    Sent from my iPhone

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