Effectiveness of Treatment with rhBMP-2 rhBMP-7 or rhBDNF in Recovery of Function Following Experimental Spinal Cord Injury in Rats**

Background Context: Therapeutics to reduce secondary injury or stimulate regeneration after spinal cord injury have yet to be employed. Bone Morphogenetic Proteins (BMPs) have potential as they are secreted in the developing nervous system and can force stem cells to differentiate into neurons or astrocytes.

Purpose: The purpose of this study was to supplement recombinant BMPs to the microenvironment of injury and measure the enhancement of locomotor recovery after SCI in rats. This study will evaluate the effectiveness of in vivo intrathecal treatments of rhBDNF, rhBMP-2, rhBMP-7 as neurotrophic factors after a spinal cord injury.

Patient Sample: Fourty-nine female Sprague-Dawley Rats (SD) ~3 month old.

Methods: Laminectomy was performed at the L2 level and a 2-0 silk suture passed ventrally underneath the spinal cord and conus medullaris. Suture ends were tied and 200 mg weights applied for 20 minutes. Rats underwent a second laminectomy at L6. where intrathecal catheter was threaded through a small needle puncture in the dura and attached to a microosmotic pump (ALZET®). The pump was implanted subcutaneously —allowing continuous infusion for 28 days of treatments with : 200ml of rhBMP-2 (0.12 µg/µl; 0.9 µg/day), rhBMP-7/ OP-1 (0.20 µg/µl; 1.4 µg/day), rhBDNF (10.00 µg/µl; 71 µg/day), saline, or glutamate 8mM. Other rats received injury with no treatment. All rats were evaluated behaviorally utilizing the Basso, Beattie, and Bresnahan (BBB) 21 point locomotor scale 2-3 times a week for 80 days by investigators blinded to their treatments. After 80 days, rats were sacrified and perfused. Spinal cord tissue sections were evaluated histologically.

Results: Athough, none of the rats completely recovered over the entire 10-week period of observation after concentric compression injury at L2, there was significant improvement in locomotor recovery over time for all rats (p<0 .0001). Recovery was only significantly lower for rhBDNF than rhBMP2 at day 80 (p<0.05) and saline from 73-80 (all p<0.05). No other significant differences among the neurotrophic factors rhBDNF, rhBMP-2, rhBMP-7 were found. rhBMP-2 treated rats had steeper recovery did BDNF rats.

Conclusions: This is the first in vivo comparative screening study of infusion of BDNF, rhBMP-2, and rhBMP-7 for locomotor recovery after SCI. In the later phases of the study, slightly greater recovery was noted for rhBMP-2 treated rats and saline rats than for the BDNF treated rats. No other differences were noted among the factors tested—all of which have independently shown neurotrophic promise.

**The FDA has not cleared a drug and/or medical device the use described in this presentation (i.e., the drug or medical device is being discussed in an “off-label" use).