Clinical Applications of Myelin Plasticity for Remyelinating Therapies in Multiple Sclerosis

Abstract

Central nervous system demyelination in multiple sclerosis (MS) and subsequent axonal degeneration represent a major cause of clinical morbidity. Learning, salient experiences, and stimulation of neuronal activity induce new myelin formation in rodents, and in animal models of demyelination, remyelination can be enhanced via experience-and activitydependent mechanisms. Furthermore, preliminary studies in MS patients support the use of neuromodulation and rehabilitation exercises for symptomatic improvement, suggesting that these interventions may represent nonpharmacological strategies for promoting remyelination. Here, we review the literature on myelin plasticity processes and assess the potential to leverage these mechanisms to develop remyelinating therapies.

Pro-myelinating Clemastine administration improves recording performance of chronically implanted microelectrodes and nearby neuronal health

“…Clemastine is an antimuscarinic compound being investigated to treat demyelinating neurodegenerative diseases [56,62,82,83,94]. Administration of Clemastine effectively promotes OPC differentiation, enhances myelination, and rescues severe symptoms of inflammatory demyelination disorders [56,[94][95][96]. To determine the impact of Clemastine on electrophysiological recording performance over the chronic timescale, C57BL/6J wildtype mice were treated with Clemastine (Fig.…”

White matter dementia then… and now

“…With respect to pathologic states, white matter plasticity is only beginning to be explored in detail, but one noteworthy report showed that neurological music therapy in patients with moderate to severe TBI produced greater white matter integrity in several right hemisphere tracts and the corpus callosum with concomitant improvement in executive function ( 100 ). Activity-dependent myelination using physical therapy and cognitive tasks is also being explored in MS patients as potential means of remyelinative therapy ( 101 ), as long-sought pharmacological approaches to remyelination have remained elusive despite decades of effort ( 102 ). Also of interest in this context is the application of non-invasive brain stimulation with modalities including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS); whereas these methods mainly target cortical gray matter, and their impact on cognition is unclear, the possibility exists that these modalities may promote white matter plasticity and hence improve cognition ( 77 ).…”

Epidermal Growth Factor Pathway in the Age-Related Decline of Oligodendrocyte Regeneration

“…Myelin increases the propagation speed of electrical signaling along the length of an axon by saltatory conduction. Moreover, myelin has numerous emerging roles that includes, providing metabolic support (Fünfschilling et al, 2007 ; Philips and Rothstein, 2017 ), memory consolidation (Pan et al, 2020 ; Steadman et al, 2020 ), task-associated learning experiences (Kato et al, 2020 ; Wang et al, 2020 ), and reviewed by (Pan and Chan, 2021 ), whilst myelin loss renders axons more vulnerable to damage (Smith, 2006 ). Once developmental myelination is complete, myelin remodeling continues throughout life via a reservoir of oligodendrocyte progenitors (OPCs) which are the main proliferating pool of cells in the adult CNS and possess the stem-cell-like feature of self-renewal (Nishiyama et al, 2021 ).…”