Multiple sclerosis (MS) is a disease where the body’s immune system impairs myelin, the protective sheath that covers nerve fibers running through the central nervous system. Damaged myelin affects communication between the brain and the rest of the body. As a result, MS can lead to irreversible disability, including difficulty walking. According to Atlas of MS, the number of people with MS across the globe was 2.9 million in 2023. This includes 0.9 million in the U.S. where over 2,000 people are diagnosed with MS every month. Today’s standard of care for the most severe cases of MS includes disease-modifying therapies, several of which unfortunately carry significant health risks.
One promising area in clinical research is the development of remyelinating therapies through both drugs and medical devices. A review of clinical trials for remyelinating drugs published recently in February of 2024, indicates that visual electrophysiology test results are the most widely used endpoints to validate drug efficacy. The identification of biomarkers of systemic diseases through the visual function is in fact a growing trend generally known as oculomics. Research to establish biomarkers for MS is part of this trend, usually through leading-edge retinal imaging approaches.
Clinical trials of promising new therapies require quantitative data to validate their efficacy. In large clinical trials, biomarkers in retinal images must be converted to quantitative measures through grading, using reading centers with trained medical professionals or through reliable machine leaning algorithms. Both methods add cost, complexity, and delays to the trials. Such a conversion step from image to quantitative data could also potentially diminish confidence in the results.
Visual electrophysiology is an alternative to imaging approaches in identifying biomarkers of systemic diseases. For MS, visual evoked potentials (VEP) are a practical and non-invasive test for evaluating MS progression and remyelinating drug efficacy. The results are quantitative, objective, and immediately available upon completion of the test, which explains why VEP has emerged as the preferred test for remyelinating drug clinical trials. Clinical trials known as RENEW, RiBUILD, and CCMR One demonstrated efficacy of their remyelinating drugs by achieving statistically significant results through VEP. Four more trials, including ReCOVER, ReWRAP, ONSTIM, and CCMR Two, are recruiting subjects and all plan on using VEP for their primary endpoint.
The myelin sheet surrounding nerve fibers is sometimes compared to insulation on electrical wires. When myelin is damaged, the nerve signal can be slowed or blocked. Conversely, remyelination reduces delays in signal transmission. VEP tests consist of presenting rapidly reversing checkerboard-pattern visual stimulus on a display monitor and recording electrical signals between frontal and occipital electrodes. In normal subjects, a positive voltage peak called P100 typically occurs 100 ms after the onset of the visual stimulus. Measurements of P100 delays provide a measure myelin loss or remyelinating drug efficacy.
One caution is that consumer liquid-crystal display (LCD) monitors produce luminous flash artifacts that can interfere with the pattern stimulus in VEP tests and invalidate them. Therefore it’s important to use display monitors designed specifically for these tests.
Remyelinating drugs may counter the effects of MS, but alone they won’t cure the disease. Significant research to establish the causes underlying the disease is ongoing. For example, research in the regulation of innate immune responses may help our understanding of the underlying mechanism of systemic diseases such as MS. Visual electrophysiology provides again a convenient way to obtain quantitative and objective data. For example, one study found through electroretinography (ERG) in mice, that microRNA is key in regulating the inflammatory profiles of microglia and macrophages, which are thought to be key actors in immune response regulation.
Visual electrophysiology diagnostic tools are widely deployed in preclinical research and clinical applications. Their ability to immediately produce objective and reliable quantitative results is driving their adoption in therapy research for MS and other systemic diseases.