Reversing age-related impairment of myelin repair - a novel therapy for MS

Project: Research

Project Details

Project Description

In multiple sclerosis (MS), chronic demyelination initiated by immune-mediated destruction of myelin, leads to axonal damage and neuronal cell death, resulting in a progressive decline in neurological function. Myelin regeneration, or remyelination, involves the generation of new myelin-forming oligodendrocytes from progenitor cells. A major impediment to myelin repair in patients with chronic MS is age-related impairment in remyelination capacity. The development of therapies that reverse the age-related decline in remyelination would be of major therapeutic benefit to MS patients.

CIA Merson has demonstrated that myelin can be regenerated from either of two distinct types of progenitor cells, namely, neural precursor cells (NPCs) residing in the subventricular zone, and oligodendrocyte progenitor cells (OPCs). In this project we will investigate the effect of ageing upon the remyelination capacity of both NPCs and OPCs and assess the potential therapeutic benefit of interventions designed to rejuvenate the remyelination process.

The project will address the following aims:

1. Establish whether ageing has differential effects on the capacity of NSCs or OPCs to remyelinate the brain after a demyelinating insult
2. Reveal how ageing influences gene expression and chromatin accessibility in OPCs and NSCs during remyelination
3. Examine whether partial reprogramming of NSCs or OPCs in aged mice can rejuvenate their capacity for efficient remyelination

The outcomes of this project will reveal the effect of age upon the remyelination capacity of OPCs versus NPCs and establish whether the age-associated decline in remyelination capacity can be reversed. The results of the project will inform the development of new therapeutic interventions to treat MS.
StatusActive
Effective start/end date1/01/2131/12/24

Keywords

  • multiple sclerosis (MS)
  • Remyelination
  • Oligodendrocytes
  • neural stem cell
  • Demyelination