Assessment of the combined effects of chondroitinase and autologous Schwann cells on hand function after cervical SCI in primates

Abstract
Introduction: Chondroitinase ABC and Schwann cells have been shown independently to promote functional recovery in rodents after contusive injury. Autologous human Schwann cells ahSC are being tested in Phase 1 clinical trials for sub-acute and chronic SCI. Recognizing the necessity of combination strategies, we are exploring the acute injection of a lentiviral transfer vector carrying a mammalian compatible engineered chABC gene (LV-chABC), with or without sub-acute aSC transplantation, in primates following unilateral C3/4 SCI. Here, we present the preliminary evaluation of the hand and arm recovery up to six months post-injury and treatment. Methods: Seven young adult male primates (Macaca fascicularis) received a right-sided hemi-contusion using the Miami Large Animal Impactor. They were randomized into: Injury only controls (n=2), Injury + 2 hours post-injury perilesional injection of LV-chABC (n=3), and Injury + LV-chABC injection + aSC transplant 14 days post-SCI (n=2). Animals were acclimatized to be comfortable within a primate chair and also provided with cage objects to promote grasp practice. They were trained to retrieve food pellets from a modified Brinkman board consisting of 20 cross-shaped slots suited to the monkeys’ fingers. The board was presented in the horizontal and vertical planes (relative to the floor) to test arm and shoulder strength, wrist rotation and thenar opposition. Both hands were exposed to the tasks equally during the pre and post injury phases.
Results: Significant differences in retrieval time and retrieval quality were found between the left (control) and right (injured) hand in each animal and between the 3 groups as of 6 months post-injury. LV-chABC injected animals showed the most rapid recovery. Additionally observed differences include the rate to reach hand function plateau and the variety of strategies developed to perform the task.
Conclusions: Animals continue to survive. The tests discriminate recovery of fine dexterity of finger movements from adaptation strategies. Deficits and recovery of combined upper and lower extremity gait coupling are assessed with treadmill kinematics.

Authors
*A. Y. FLORES1, A. J. SANTAMARIA1, R. DE NEGRI1, F. D. BENAVIDES1, N. D. JAMES4, Y. NUNEZ-GOMEZ2, J. P. SOLANO2, J. VERHAAGEN5,6, E. J. BRADBURY4, J. D. GUEST1,3;
1Miami Project to Cure Paralysis, 2Pediatric Critical Care, 3Neurolog. Surgery, Univ. of Miami, Miller Sch. of Med., Miami, FL; 4The Wolfson Ctr. for Age-Related Dis., King’s Col., London, United Kingdom; 5Lab. for Neuroregeneration, Netherlands Inst. for Neurosci., Amsterdam, Netherlands; 6Ctr. for Neurogenomics and Cognition research, Vrije Univ. Amsterdam, Amsterdam, Netherlands
Disclosures
A.Y. Flores: None. A.J. Santamaria: None. R. de Negri: None. F.D. Benavides: None. N.D. James: None. Y. Nunez-Gomez: 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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