Repeated courses of granulocyte colony‐stimulating factor in amyotrophic lateral sclerosis: Clinical and biological results from a prospective multicenter study

Abstract

Granulocyte colony-stimulating factor (G-CSF) induces a transient mobilization of hematopoietic progenitor cells from bone marrow to peripheral blood. Our aim was to evaluate safety of repeated courses of G-CSF in patients with amyotrophic lateral sclerosis (ALS), assessing disease progression and changes in chemokine and cytokine levels in serum and cerebrospinal fluid (CSF). Twenty-four ALS patients entered an open-label, multicenter trial in which four courses of G-CSF and mannitol were administered at 3-month intervals. Levels of G-CSF were increased after treatment in the serum and CSF. Few and transitory adverse events were observed. No significant reduction of the mean monthly decrease in ALSFRS-R score and forced vital capacity was observed. A significant reduction in CSF levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-17 (IL-17) was observed. G-CSF treatment was safe and feasible in a multicenter series of ALS patients. A decrease in the CSF levels of proinflammatory cytokines MCP-1 and IL-17 was found, indicating a G-CSF-induced central anti-inflammatory response.

Stem Cell Therapy for Amyotrophic Lateral Sclerosis

“…Subsequently, a number of clinical trials have evaluated autologous MSC transplantation and demonstrated that intraspinal, intrathecal, and intracerebral transplants were safe and feasible [54]. It is worth mentioning that three clinical studies innovatively mobilized endogenous MSCs by using granulocyte-colony stimulating factor (G-CSF) in ALS patients, and their MSCs were instantaneously increased and no major adverse events were found in any of the three studies [55][56][57]. Moreover, BrainStorm Cell Therapeutics developed a cell type trademarked as "NurOwn™" for the treatment of ALS.…”

Cytokine Therapies in Neurological Disease

“…Several small studies [20,21] have demonstrated feasibility of G-CSF administration without significant change in clinical outcome measured by the ALS functional rating scale. Preliminary diffusion tensor imaging results suggested white matter tract preservation with treatment [21].…”

Recent Advances and the Future of Stem Cell Therapies in Amyotrophic Lateral Sclerosis

“…Another study in 17 patients comparing subcutaneous G-CSF with a placebo control arm showed elevated CD34+ PBSCs, but no difference in disease progression [62]. Similarly, the STEMALS trial utilized subcutaneous G-CSF along with a 5-day course of mannitol with the hopes of increasing permeability across the blood-brain barrier in 26 patients [63,64]. Again, there was an increase in circulating CD34+ PBSCs, and in this trial a decrease in the proinflammatory cytokines monocyte chemoattractant protein-1 and interleukin-17, but no change in ALSFRS-R.…”