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Targeting SMOX Preserves Optic Nerve Myelin, Axonal Integrity, and Visual Function in Multiple Sclerosis

Harry O Henry-Ojo1,2,3, Fang Liu1,2,3, S Priya Narayanan1,2,3

  • 1Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30907, USA.

Biomolecules
|February 26, 2025
PubMed

Insights

Inhibiting spermine oxidase (SMOX) with MDL72527 protected myelin and axons, improving visual function in a multiple sclerosis model. This suggests SMOX inhibition is a promising therapeutic strategy for demyelinating diseases.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Multiple sclerosis (MS) is a disabling neurological disease characterized by inflammation, demyelination, and axonal damage.
  • Previous research indicated that inhibiting spermine oxidase (SMOX) with MDL72527 reduced symptoms and damage in an MS model (EAE).

Purpose of the Study:

  • To investigate the therapeutic potential of SMOX inhibition for myelin preservation, axonal integrity, and visual function in the EAE model.
  • To explore the role of galectin-3 (Gal3) in SMOX-mediated neuroprotection.

Main Methods:

  • Electron microscopy and immunofluorescence were used to assess myelin and axonal integrity in the optic nerve of EAE mice treated with MDL72527.
  • Quantitative analysis of g-ratio and axon count metrics.
  • Electroretinography (ERG) was performed to evaluate retinal ganglion cell (RGC) function and axonal conduction.
  • Western blotting or similar techniques were used to assess Gal3 expression.

Main Results:

  • SMOX inhibition with MDL72527 significantly preserved myelin thickness and axonal integrity in the optic nerve.
  • Quantitative metrics (g-ratio, axon count) showed significant improvement in MDL72527-treated EAE mice.
  • Functional assessments via ERG demonstrated improved RGC function and axonal conduction.
  • SMOX inhibition led to downregulation of galectin-3 (Gal3) expression.

Conclusions:

  • SMOX inhibition effectively preserves myelin and axons, improving visual function in the EAE model.
  • The findings support SMOX inhibition as a potential therapeutic strategy for multiple sclerosis and other demyelinating disorders.
  • Galectin-3 may play a role in the neuroprotective effects of SMOX inhibition.
Keywords:
MDL72527multiple sclerosismyelinoptic nervespermine oxidasevision

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