Regulatory T cells for amyotrophic lateral sclerosis/motor neuron disease: A clinical and preclinical systematic review

J Cell Physiol. 2020 Jun;235(6):5030-5040. doi: 10.1002/jcp.29401. Epub 2019 Dec 1.

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by neuronal degeneration and inflammation in the nerves. The role of the immune system has been concentrated by researchers in the etiopathogenesis of the disease. Given the inhibitory roles of regulatory T cells (Tregs), it is expected that increasing or activating their populations in patients with ALS can have significant therapeutic effects. Here we searched databases, including CENTRAL, MEDLINE, CINAHL Plus, clinicaltrials.gov, and ICTRP for randomized clinical trials (RCTs) and non-RCTs until March 2019. For preclinical studies, we searched PubMed, Scopus, and Google Scholar up to June 2019. We also included preclinical studies, due to the lack of clinical information available, which used Tregs (or directly targeting them) for treating mice models of ALS. We identified 29 records (CENTRAL 7, MEDLINE 4, CINAHL Plus 8, and clinicaltrials.gov 10) and removed 10 duplicated publications. After screening, we identified one RCT which had been published as an abstract, three non-RCTs, and four ongoing studies. We also identified 551 records (PubMed 446, Google Scholar 68, and Scopus 37) for preclinical studies and performed a meta-analysis. Finally, we found three papers that matched our inclusion criteria for preclinical studies. Results indicated the effectiveness of the application of Tregs in the treatment of ALS. Our meta-analysis on preclinical studies revealed that Tregs significantly prolonged survival in mice models of ALS. Overall, our analysis testified that exertion of Tregs in the treatment of ALS is a promising approach, that notwithstanding, requires further evaluations.

Keywords: amyotrophic lateral sclerosis; motor neuron disease; preclinical study; randomized controlled trial; regulatory T cells.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / immunology*
  • Amyotrophic Lateral Sclerosis / pathology
  • Humans
  • Inflammation / immunology*
  • Inflammation / pathology
  • Motor Neuron Disease / genetics
  • Motor Neuron Disease / immunology*
  • Motor Neuron Disease / pathology
  • Motor Neurons / immunology
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • Quality of Life
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology