Mesenchymal stem cells in Amyotrophic Lateral Sclerosis

Currently, there is no treatment for Amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease that targets motor neurons causing premature death. Mesenchymal stem cells (MSCs) might be suitable for cell therapy in ALS because of their immunomodulatory and protective properties. The administration of bone marrow (BM)-derived MSCs has led to beneficial effects in animal models for several neurodegenerative diseases, such as in SOD1-G93A mice, where expanded MSCs can survive and migrate after transplantation and prevent astrogliosis and microglial activation. We performed two Phase I trials (in 2001 and 2003) for the assessment of the feasibility and toxicity of transplantation of autologous MSCs into the spinal cord in ALS patients. The trials, approved and monitored by the National Institute of Health and by the Ethics Committees, enrolled 19 ALS patients (11 M and 8 F). Patients were followed up for 6-9 months and then treated with autologous BM-MSCs. In addition to the clinical measures, we also analyzed behavioral and quality of life changes. Eight patients died and 6 patients underwent tracheostomy for respiratory failure after a mean survival time of All deaths or tracheostomy were deemed to be unassociated with the experimental treatment. The most important result of our studies is the demonstration of the lack of tumor formations or abnormal cell growth. All patients well tolerated the procedure, the side effects related to the surgery were mild and transient, and there was no deterioration in psychosocial status of patients. Our results showed the safety of MSC transplantation in the central nervous system during a follow-up of nearly 12 years, supporting the MSC-based therapy for neurodegenerative disorders. More recent studies showed that the administration of human MSCs in the cisterna lumbaris of SOD1 G93A mice, providing evidence that this injection can exert strongly positive effects and could be used in outpatient surgery.