Lecture to ASIA (American Spinal Injury Association), Denver, 14-16/05/2004

An open label study of autologous incubated macrophages in patients with acute complete spinal injury

Nachshon Knoller¹, M.D.; Moshe Hadani¹, M.D.; Valentin Fulga², M.D; Gabriel Zelig³, M.D.; Josef Attias⁴, Ph.D.; Gustavo Auerbach², D.M.D.; David Snyder², Ph.D.; Ronit Bakimer², Ph.D.; Zvi H. Rappaport5, M.D.; Eti Yoles^2,6, Ph.D.; Michael Belkin⁷, M.D.; Michal Schwartz⁶, Ph.D.

¹Department of Neurosurgery, Chaim Sheba Medical Center, Tel-Hashomer, Israel

²Proneuron Biotechnologies, Ness-Ziona, Israel

³Department of Neurological Rehabilitation, Chaim Sheba Medical Center, Tel-Hashomer, Israel

⁴Institute for Clinical Neurophysiology & Audiology, Schneider Children's Medical Center of Israel, Petach-Tikva, Israel

⁵Department of Neurosurgery, Rabin Medical Center, Petah Tiqva, Israel.

⁶Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel

⁷The Goldschleger Eye Institute, Tel-Aviv University and Sheba Medical Center, Tel-Hashomer, Israel

OBJECTIVES: This Phase I, open label non-randomized study was designed to assess the safety and tolerability of autologous incubated macrophages administered to patients with acute complete spinal injury.  

METHODS: The treatment consisted of preincubating macrophages with autologous dermis, then injecting them into the spinal cord during laminectomy within 14 days post-injury.    Patients were evaluated preoperatively and 3, 6, and 12 months after treatment.  Neurological completeness was established according to ASIA standards and all patients had a conclusive and stable ASIA A classification at baseline. Follow-up assessments included safety monitoring, ASIA Impairment Scale, motor and sensory scores, FIM, bladder and bowel function, sensory and motor evoked potentials and MRI. Initially, eight patients were recruited and 12 months follow-up was completed. Later, four additional patients were treated and follow-up is ongoing.  

RESULTS: Of the first eight patients, three converted from ASIA A to C. Of the patients who remained ASIA A, three showed varying degrees of increase in sensory scores, as well as improved signs of somatosensory evoked potentials, objective evidence of restored nerve conduction.  Of the later patients still in follow-up, one has recently converted to ASIA B. There were no adverse events attributed to the implantation of autologous macrophages.  

CONCLUSIONS: Administration of autologous macrophages is well tolerated with no evidence of therapy-related adverse events. The neurological outcomes are considered significantly better than expected outcomes for patients with similar injuries.  Further clinical development of autologous macrophages in the treatment of patients with acute SCI is supported by this study.