A targeted extracellular vesicles loaded with montelukast in the treatment of demyelinating diseases

Biochem Biophys Res Commun. 2022 Feb 26:594:31-37. doi: 10.1016/j.bbrc.2022.01.051. Epub 2022 Jan 15.

Abstract

The main pathological characteristics of demyelinating diseases are central nervous system (CNS) myelin damage, and the differentiation of oligodendrocyte precursor cells is the therapeutic target of myelin repair. Previous studies have found that a large number of platelet-derived growth factor receptor α(PDGFRα) positive oligodendrocyte progenitor cells (OPCs) accumulate in the lesion area of myelin injury, and differentiation is blocked. However, the therapeutic effects of drugs currently used clinically on OPCs differentiation and myelin repair are limited. The main reason is that it is difficult to reach the effective concentration of the drug in the lesion area. Therefore, efficiently delivering into the CNS lesion area is of great significance for the treatment of MS. Natural exosomes have good biocompatibility and are ideal drug carriers. The delivery of drugs to lesion areas can be achieved by giving the exosomes armed targeting ligand. Therefore, in this study, combining exosomes with PDGFA helps them accumulate in OPCs in vitro and in vivo. Further, load montelukast into exosomes to achieve targeted therapy for cuprizone-induced demyelination animal model. The implementation of this research will help provide effective treatments for demyelinating diseases and lay a theoretical foundation for its application in the clinical treatment of different demyelinating diseases.

Keywords: Cuprizone-induced demyelination; Exosomes; Montelukast; Remyelination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / pharmacology*
  • Animals
  • Cell Differentiation / drug effects
  • Cell Lineage
  • Cuprizone
  • Cyclopropanes / pharmacology*
  • Demyelinating Diseases / metabolism*
  • Disease Models, Animal
  • Drug Delivery Systems
  • Exosomes / metabolism
  • Extracellular Vesicles / metabolism*
  • In Vitro Techniques
  • Ligands
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myelin Basic Protein / metabolism
  • Myelin Sheath / metabolism
  • Neurons / metabolism
  • Oligodendrocyte Precursor Cells / metabolism
  • Oligodendroglia / metabolism
  • Phagocytosis
  • Quinolines / pharmacology*
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism*
  • Regeneration
  • Stem Cells / metabolism
  • Sulfides / pharmacology*

Substances

  • Acetates
  • Cyclopropanes
  • Ligands
  • Myelin Basic Protein
  • Quinolines
  • Sulfides
  • Cuprizone
  • Receptor, Platelet-Derived Growth Factor alpha
  • montelukast