# Targeting spermine oxidase to prevent vision loss in Multiple Sclerosis

> **NIH VA I01** · CHARLIE NORWOOD VA MEDICAL CENTER · 2022 · —

## Abstract

PROJECT SUMMARY
Multiple sclerosis (MS) is a highly disabling neurological disease affecting veterans, characterized by
demyelination, inflammatory responses and neurodegeneration. Current medications available for treating MS
are only partially effective as they specifically target the inflammatory phase, but not the neurodegenerative
phase, and therefore have limited effects on long-term disability. Increasing evidences suggest that
neurodegeneration plays a crucial role in the MS pathology. However, the mechanisms underlying the
progressive neurodegeneration are poorly studied in MS. Hence, there is a great need for identifying new agents
that target the neurodegenerative stage of the disease. Our goal is to contribute to the treatment of MS, by
defining the specific role of Spermine Oxidase (SMOX, an important enzyme in polyamine metabolic pathway),
in mediating neurodegeneration in the MS retina and by demonstrating its potential as a therapeutic target for
MS treatment. Our central hypothesis is that SMOX is upregulated in retinal neurons, resulting in increased
polyamine oxidation and release of acrolein in the MS retina. Our hypothesis predicts that formation of various
protein-acrolein adducts causes oxidative damage in the retina, leading to neuronal dysfunction. Our objectives
are: 1) characterize molecular mechanisms involved in SMOX-induced neuronal damage in the experimental
model for MS; 2) determine the impact of SMOX overexpression/downregulation in mediating neurodegeneration
in the experimental model of MS; and 3) determine the therapeutic potential of inhibiting SMOX for the treatment
of MS. Our expected outcomes include 1) identification of SMOX induced molecular changes by which
neuronal damage occurs in MS; 2) demonstration of alterations in retinal neuronal survival and function in
response to manipulation of SMOX expression in the experimental model; and 3) preservation of visual acuity,
contrast sensitivity, retinal structure and reduced inflammation in response to SMOX blockade. Our studies will
impact the field of MS by providing new and significant information on mechanisms by which neurodegeneration
occurs in MS, and thus can lead to the development of accurate and efficacious targeted therapies to improve
the quality of life in veterans affected by the disease. Results coming out these studies may provide translational
strategies for MS disease progression and can also be applicable to cognitive, behavioral and motor deficits in
MS patients. Retina is known as “window to the brain” and hence targeting SMOX function has the potential to
be evaluated as therapy for MS in general and is also applicable to other disabling diseases affecting veterans
such as Traumatic brain injury, Parkinson’s disease and spinal cord injury.

## Key facts

- **NIH application ID:** 10257895
- **Project number:** 1I01BX005193-01A1
- **Recipient organization:** CHARLIE NORWOOD VA MEDICAL CENTER
- **Principal Investigator:** Priya Narayanan
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-10-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10257895

## Citation

> US National Institutes of Health, RePORTER application 10257895, Targeting spermine oxidase to prevent vision loss in Multiple Sclerosis (1I01BX005193-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10257895. Licensed CC0.

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