New tools to better understand test therapies in progressive MS

Project Summary:

The neurological problems that people with MS experience are related to both inflammation and neurodegeneration.

Working together, two teams will combine expertise to develop and validate the utility of four different methods to measure disease progression, including inflammation and neurodegeneration, in MS - ocular coherence tomography (OCT), evoked potentials (EP), neurofilaments in serum (Nf) and magnetic resonance imaging (MRI).

The visual system is an ideal model for monitoring neurodegeneration, neuroprotection, and remyelination in multiple sclerosis (MS). The retina, in the back of the eye, can be examined by OCT using a light beam, which allows one to measure the thickness of the retinal nerve fiber layer, and to monitor changes over time. OCT is inexpensive, reproducible, well tolerated, non-invasive, and easily repeatable. The goal of this part of the project is to establish the visual system as a model within which to monitor neurodegeneration, disease progression, neuroregeneration and neuroplasticity in PMS, both for tracking patients, as well as outcome measures in clinical trials.

The second tool that will be used, evoked potentials, measure the latency (delay) of the reponse to a stimulus, which can be applied as a checkerboard to the eye, as a small current to the wrist or ankle or as a magnetic impulse to the skull. In this way, the functional integrity of the visual, sensory and/or motor systems can be measured.

The third tool, the measurement of neurofilament in the blood, is possible due to the fact that when nerve cells and fibers decompose certain proteins are secreted, and Nf can be measured when this occurs.

Finally, MRI can show lesions and with that the integrity of the tissue and the volume of the brain and grey matter can be measured.

Each of these methods has been shown to correlate to clinical disability, and some also predict disease progression. Furthermore, they are used in routine clinical examinations with a very low risk of side-effects. In sum, more precise tools to quantify disease progression may allow investigators to perform clinical studies more efficiently.