Abstract
The need for remyelinating drugs is essential for healing disabling diseases such as multiple sclerosis (MS). One of the reasons for the lack of this class of therapies is the impossibility to monitor remyelination in vivo, which is of utmost importance to perform effective clinical trials. Here, we show how optical coherence tomography (OCT), a cheap and non-invasive technique commonly used in ophthalmology, may be used to assess remyelination in vivo in MS patients. Our pioneer approach validates OCT as a technique to study remyelination of the optic nerve and reflects what is occurring in non-accessible central nervous system (CNS) structures, like the spinal cord. In this study we used the orally bioavailable small molecule VP3.15, confirming its therapeutical potential as a neuroprotective, anti-inflammatory, and probably remyelinating drug for MS. Altogether, our results confirm the usefulness of OCT to monitor the efficacy of remyelinating therapies in vivo and underscore the relevance of VP3.15 as a potential disease modifying drug for MS therapy.
Highlights
Multiple sclerosis (MS) is the most common primary demyelinating disease and neurological condition affecting young adults, with about 2.5 million people currently diagnosed around the world [1]
To the best of our knowledge, this is the first work that correlates the morphological characteristics of optic nerve in vivo (OCT) with demyelination/neurodegeneration and remyelination in an animal model of multiple sclerosis (MS), through histological analysis performed at the endpoint of the study
Some of our findings, such as the decreased thickness of retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) in MS have already been described [43,44,45]. These studies were not repeated at different times of evolution, nor were corroborated with postmortem observations, conferring to our present study part of its uniqueness
Summary
Multiple sclerosis (MS) is the most common primary demyelinating disease and neurological condition affecting young adults, with about 2.5 million people currently diagnosed around the world [1]. It is characterized by glial cell pathology (especially oligodendrocytes and their precursors), demyelination, inflammatory processes, and axonal damage in the central nervous system (CNS) [2]. The efficacy of remyelinating therapies is difficult to assess in vivo due to the technical limitations in exploring the CNS, in clinical trials and in preclinical studies where MS animal models are used
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