53rd National Congress of the Italian Society of Neurosurgery, Milan, November 21-24, 2004

AUTOLOGOUS MACROPHAGE THERAPY FOR PATIENTS WITH COMPLETE SCI: RESULTS OF PHASE I TRIAL AND PREVIEW ON THE PHASE II TRIAL

Claudio Bernucci, Nachshon Knoller¹,Jacques Brotchi², David Snyder³
Dipartimento di Neurochirurgia, H San Raffaele, Milano
¹Chaim Sheba Medical Center, Tel Hashomer, Israel
² Erasme Hospital, Brussels, Belgium
³Proneuron Biotechnologies, Ness-Ziona, Israel

Complete spinal cord injury (SCI) leads to irreversible motor and sensory functional loss. Up to now no surgical or medical therapy is available for these patients. The last clinical trial designated for SCI has been NASCIS I and II, and its results are still matter of debate.

An international randomized clinical trial with ProCord therapy is underway in Israel and USA.

ProCord consists of autologous macrophages that have been incubated with skin. Macrophages and other immune cells participate in normal wound healing in most tissues, but their activity in the damaged central nervous system is repressed by “immune privilege”. Injection of the skin-coincubated macrophages into the damaged spinal cord is designed to overcome the hostile tissue environment, thereby promoting neuronal survival and regrowth. Experiments showing CNS regeneration and partial functional recovery in rats (Rapalino et al, Nature Medicine 4:814-821, 1998) served as proof of principle. Safety and efficacy have been demonstrated in extensive preclinical experiments that continue to produce promising results.

A Phase I open label, non-randomized clinical trial was undertaken at Sheba Medical Center, Israel and Erasmus Hospital, Brussels, Belgium. Fourteen SCI patients (C5-T11) diagnosed as ASIA A (American Spinal Injury Association) at baseline were treated with ProCord 9 to 15 days after injury. Three patients recovered motor and sensory neurological function improving from ASIA A to ASIA C, one with recovered voluntary bladder control. An additional patient recovered sensory function with no motor recovery (ASIA B). Three other patients showed improvements in neurological sensory scores but remained ASIA A. The greatest gains occurred during the first year.

Despite the small study size (14 patients), recovery of clinically significant neurological function has been observed in several subjects after Procord treatment, whereas untreated patients with complete SCI rarely recover significant function. Thus, ProCord appears to be a potentially valuable therapy in the acute stage for improving outcomes after SCI.

The Phase II trial will enroll 61 ASIA A patients, 39 in the treatment group and 22 in the control group. Improvement in the ASIA classification of at least one grade by 12 months is the primary efficacy endpoint, while the secondary efficacy endpoints are recovery of ASIA sensory and motor scores, recovery of at least two motor levels (in cervical patients), and recovery of bladder and bowel function.

Since the administration of the activated macrophages must be performed within two hours from its release the production facility needs to be adjacent to the treating medical center, Therefore, only few centers have been established for the Phase II trial and every patient has to be referred to them.Our Institution will  collaborate with Proneuron collecting and screening potential candidates for the trial and will review the patient at follow-up as an independent investigator.