Proneuron Biotechnologies: Treatment for Spinal Cord Injury and other Neurological Disorders

Poster at National Neurotrauma Society Symposium, San Diego, 21-22 October 2004

AUTOLOGOUS SKIN-COINCUBATED MACROPHAGES, A CELL THERAPY FOR ACUTE SPINAL CORD INJURY: TRANSLATION OF PRECLINICAL DEVELOPMENT FOR THE CLINIC

Marder JB, Bomstein Y, Vitner K, Smirnov I, Yoles E, Snyder DA
Proneuron Biotechnologies, P. O. Box 277, Ness Ziona, 74101, Israel

Autologous Skin-coincubated Macrophages are being developed as a cell therapy for spinal cord injury. The rationale for the therapy is to induce controlled immune activities that promote survival and repair of the injured nerve tissue. Preclinical experiments were performed using macrophages prepared from the blood of spinally-contused donor rats, incubated with skin tissue, and then implanted into the spinal cords of spinally-contused recipient rats. The cells were administered by microinjection into the spinal mesenchyma. Control spinally-contused rats were injected with medium only. Experiments were performed to determine the optimal cell dose and the optimal site for injection. Rats were assessed by their recovery of locomotor function. The dose-response indicated that low and high doses were less effective than intermediate doses. The most effective injection site was immediately caudal to the spinal lesion, suggesting that the implanted cells exert their effects only locally, and do not migrate.

The optimal preclinical treatment defined above has been translated for clinical use. A protocol was developed to manufacture human Autologous Skin-coincubated Macrophages with similar properties to the rat cells, and an appropriate administration protocol were developed. Where rat spinal cords (2-3 mm diameter) were injected with a single microinjection, the protocol for humans (cord diameter 10-14 mm) is to give multiple injections across the full width of the cord, immediately caudal to the lesion. The cell dose for each injection is the same as the optimal single-injection dose in the rat, though the total dose is increased several-fold because of the multiple injections. An international Phase II clinical trial is now underway to test the therapy in patients with acute, complete spinal cord injury.