Safety and Feasibility of G-CSF Compassionate use in ALS Patients (P6.009)

OBJECTIVE: G-CSF may compensate rapid neuronal loss in ALS. Therefore we initiated long-term compassionate use of G-CSF in ALS patients. BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) is a long-term established and safe hematopoietic growth factor. It is neuroprotective, increases neurogenesis and induces neuronal differentiation. Despite evidence for efficacy in ALS animal models, multiple small trials with G-CSF in patients delivered inconclusive results. Functional improvement might have been missed due to inadequate application and duration of treatment with short follow up. DESIGN/METHODS: 23 ALS patients (15 male, 8 female, mean age 51,4 yrs. (±13.2), mean ALS-FRS-r at start 36.75 (± 6.84)) were treated with G-CSF 5-10 μg/kg BW s.c. plus standard treatment incl. Riluzole. Application modes were individually adapted with (1) G-CSF for five consecutive days every four weeks (mean: 26.3 treatment months (8 - 49)) or (2) G-CSF twice a week (mean 23.2 treatment months (8 - 31)). Monthly control visits with clinical exams, ALSFRS-r, clinical chemistry, blood smears, bone marrow function were performed. RESULTS: Compliance was excellent, aside from mild to moderate bone pain in all patients, application modes were well tolerated. Both modes of delivery resulted in hematopoietic stem cell mobilization and biomarker modulation. We found no evidence of premalignant changes in bone marrow differentiation. In retrospective analysis a significant decrease in ALS progression rate - ALS-FRS-r - and clinical relevant prolongation of overall survival in comparison to the current Pro-ACT database, indicate high safety of prolonged G-CSF treatment. CONCLUSIONS: Long-term administration of G-CSF in ALS patients is safe and feasible. Compliance of outpatient regimens is excellent. A prospective trial is very urgently needed. Disclosure: Dr. Khomenko has nothing to disclose. Dr. Baldaranov has nothing to disclose. Dr. Johannesen has nothing to disclose. Dr. Kobor has nothing to disclose. Dr. Blume has nothing to disclose. Dr. Bruun has nothing to disclose. Dr. Grassinger has nothing to disclose. Dr. Kammermaier has nothing to disclose. Dr. Ludolph has nothing to disclose. Dr. Deppe has nothing to disclose. Dr. Schuierer has nothing to disclose. Dr. Schulte-Mattler has nothing to disclose. Dr. Friede has nothing to disclose. Dr. Laage has nothing to disclose. Dr. Schneider has nothing to disclose. Dr. Bogdahn has nothing to disclose.