Neural Stem Cells Transplantation as a Neuroprotective Strategy for Amyotrophic Lateral Sclerosis (ALS) (2016)

Introduction Amiotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a prevalence rate of up to 7.4/100,000 and the overall risk of developing ALS over a lifetime is 1:400. Most patients die from respiratory failure following a course of progressive weakness. There is no effective therapy. Novel therapeutic strategies might be directed at replacing or repairing the damaged motor neurons; Cell therapy is emerging as a potential therapeutic option in ALS. The primary objective of our study was to verify the safety and tolerability of transplantation of human fetal neural stem cells (hNSCs) directly into the spinal cord of humans. The study was approved by the SuperiorNational Health Institute. Material and Methods 18 patients with definite ALS were recruited and treated. Patients were included if they had ALS of spinal onset with severe functional impairment of the lower limbs and mild functional impairment of the upper limbs without signs of respiratory failure. The patients were monitored by clinical evaluation which included the ALS-FRS scale, Norris score, bulbar score, and MRC strength scale. Respiratory assessment included clinical evaluation, pulmonary function tests, arterial blood gases analysis, and nocturnal cardio-respiratory monitoring. Neurophysiological assessments were made including EMG, and somatosensory evoked potentials. The neuroradiological assessment consisted of MRI of spinal cord and brain before and after Gadolinium DTA infusion. A clinical psychologist performed psychological evaluation including an interview and psychological tests. Human fetal brain tissue specimens, all derived from the forebrain, were routinely collected from fetuses at gestational ages greater than the 8th post-conceptional week. They were immediately dissected and used to generate hNSC lines under sterile conditions. Dissociation of brain tissue, primary culturing and cell propagation were performed according to the procedure described previously by Vescovi and colleagues. Six patients received hNSCs microinjections into the dorsal (T7-T9) cord tract (3 of them received unilateral hNSCs microinjection while the remaining ones received bilateral microinjections); the other twelve patients received hNSCs microinjections into the cervical (C5-C6) cord tract (3 of them received unilateral hNSCs microinjection while the remaining ones received bilateral microinjections). Results No patients manifested severe adverse events such as death, respiratory failure or permanent post-surgical neurological deficits. Minor adverse events were: intercostal pain (2 patients) which was reversible after a mean period of 3 days after surgery, arm and leg sensory dysesthesia (6 patients) which was reversible after a mean period of 6 weeks after surgery. No patient manifested bladder and bowel dysfunction, or arm and leg motor deficit. All patients showed a good acceptance of the procedure and no significant modifications of the psychological status or quality of life were observed. Conclusions Our results appear to demonstrate that the procedures of fetal stem cells transplantation into the spinal cord of humans are safe and well tolerated by ALS patients. The minimal side effects and the absence of detrimental effects on neurological function support further research in stem cell transplantation in carefully monitored patients with ALS.