Effectiveness of Mesenchymal Stem Cell Therapy in Patients With Amyotrophic Lateral Sclerosis

Abstract

Background & Objectives: Amyotrophic lateral sclerosis is a late-onset neurodegenerative disease characterized by progressive muscle weakness and atrophy followed by eventual paralysis, leading to death within 3 years of diagnosis. Although lots of drugs targeting on anti-inflammatory and anti-apoptotic effects on central nervous system had been studies, there is no effective therapy on ALS. Additionally, riluzole (glutamate antagonist), proved by FDA, has been reported that its effect is minimal with only survival prolongation of 3 to 4 months. To date, stem cell research has highlighted ALS as a target disease for stem cell treatment. Because of its properties with various cytokines and growth factors secretion, mesenchymal stem cells (MSCs) have been focused as a neuroprotective therapy rather than substitution for motor neuron loss. We aimed to determine whether MSCs therapy is safe and effective in slowing disease progression in patients with ALS.

Method: Twenty-one patients were enrolled for our study. Clinical diagnosis was based on El Escorial criteria. MSCs were extracted from autologous bone marrow, and ex vivo expanded for about 4 weeks. Expanded MSCs were injected through intrathecal route via L2-3 space twice at an interval of 4 weeks. ALS functional rating scale-revised was used as a primary scale for the evaluation of treatment effect. All symptoms and signs provided by patients were recorded. With lead-in 3 months period, patients were followed up for 6 months after the first treatment. As a primary efficacy measurement, the score changes of ALSFRS-R before and after treatment were used.

Results: Compared with the ALSFRS-R score change during lead-in period, MSCs therapy could reduce the score change during 1st half follow up period statistically. These disease modifying effects were observed in 11 patients among total 21 ALS patients. Moreover, immediate beneficial effects such as improvement of muscle power, breathing stabilization, decreased drooling and spasticity, were observed in 13 patients. No significant adverse events were noted except minor meningeal irritation signs spontaneously resolved.

Conclusion: Disease modifying with slowing down the disease progression has not been reported yet. Moreover, there are no serious adverse events in our study. Therefore, MSCs therapy with intrathecal injection could provide an effective choice for ALS.