# Early Visual Biomarkers of Relapse and Rehabilitation in Multiple Sclerosis

> **NIH VA I01** · IOWA CITY VA MEDICAL CENTER · 2020 · —

## Abstract

Optic neuritis is an associated pathology of MS, and is often the first symptom of the disease. Even in MS
patients without any known episodes of optic neuritis, there is evidence that functional and structural
manifestations of MS in the anterior visual pathway can be detected and monitored in vivo, reflecting disease
activity. These include contrast sensitivity, critical flicker fusion frequency, evoked potentials from the retina
and brain, and inner retinal layer thickness using optical coherence tomography (OCT). Our main purpose is to
establish sensitive biomarkers of visual function that can be made widely available to veterans suffering from
MS for detecting MS relapses, progression and treatment effects. An important secondary rehabilitation goal is
to determine which conventional and new experimental treatment could decrease fluctuation in visual and CNS
function, which are known to impact quality of life, in preclinical animal models of MS.
We will employ two relevant animal models of MS, a MOG-induced experimental autoimmune
encephalomyelitis (EAE) model for chronic MS and PLP-induced EAE to mimic the relapsing-remitting form.
We will also include a heat-induced stress test to trigger fluctuations in visual and CNS function in EAE mice.
We will determine in vivo ocular structural and functional biomarkers and will correlate them with motor-
sensory and cognitive function. Data will be related to ex vivo structural manifestations of MS, namely neuron
loss and demyelination. We propose that the number of remaining neurons and their myelin integrity will
correlate with changes in optic nerve conduction speed, visual acuity and retinal nerve fiber layer thinning. We
will then examine if current treatments using Fingolimod, 4-aminopyridine and a ketogenic diet increase neuro-
axonal electrical activity and decrease functional fluctuation to favor increased rehabilitation. Newer
experimental therapies, derived from compounds hypothesized to mediate the therapeutic effects of
mesenchymal stem cell (MSC) therapy, which targeting improved nerve transduction, will also be tested in the
chronic and relapsing remitting models of MS.
Supported by pilot data results, we will determine with additional rigor that decreased optic nerve conduction
velocity precedes motor-sensory and structural deficits in the EAE model and represents an early marker of
disease activity. Our expected data will provide insights on how impairment of visual function corresponds to
demyelination, retinal thinning and retinal ganglion cell (RGC) loss. We also determine at what time point an
earlier treatment intervention will improve long-term functional and structural outcome. We further expect to
provide convincing data that improvement of neuro-axonal electrical activity and conduction speed represent
promising, new therapeutic avenues with extraordinary clinical impact for restoring function and quality of life.
Clinical translation of these results will help predict MS r...

## Key facts

- **NIH application ID:** 9972765
- **Project number:** 5I01RX002978-02
- **Recipient organization:** IOWA CITY VA MEDICAL CENTER
- **Principal Investigator:** RANDY H. KARDON
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972765

## Citation

> US National Institutes of Health, RePORTER application 9972765, Early Visual Biomarkers of Relapse and Rehabilitation in Multiple Sclerosis (5I01RX002978-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9972765. Licensed CC0.

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