Combating disorders of CNS myelination

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https://research.brighton.ac.uk/en/projects/combating-disorders-of-cns-myelination

established December 2023

 

Over 100,000 people in the UK and approximately 2.5 million people worldwide are diagnosed with Multiple Sclerosis. Currently-approved drugs to treat MS are anti-inflammatory immunomodulators and only slow disease progression. There is no cure for MS. There is an urgent need to develop new drugs to combat the secondary progressive loss of neurons and eventual failure of remyelination that occurs as the disease progresses.

To achieve this, we tackle the challenge of enhancing central nervous system (CNS) regeneration using mixed primary neuron/glial cell assays and ex vivo brain slice culture models. This enables us to screen for compounds that promote developmental myelination and CNS regeneration following injury. By deciphering the mechanisms of action of novel myelin-repair and neuroprotective drugs, this facilitates the discovery of lead compounds which we will test in vivo and expedite their translation to clinical trial.

Project timeframes

This project began in 2015 and is ongoing.

Project aims

The aim of this project is to promote functional recovery of CNS neurons following acute traumatic and/or chronic inflammatory injury. Our goal is to identify new molecular targets and develop novel therapeutics that promote:

  • neuroprotection,
  • neuroregeneration and
  • remyelination of damaged CNS tissue

The primary focus of this project is to discover new regenerative treatments for neuroinflammatory disorders of the brain and spinal cord, such as Multiple Sclerosis (MS). Myelin-forming glial cells that wrap and insulate neurons become damaged in MS and this renders axons exposed and vulnerable to degeneration. This demyelination and eventual loss of axons is what leads to the debilitating symptoms of MS, including blurred vision, fatigue, limb weakness and problems with balance.

Neurons of the adult CNS generally display very limited regeneration after injury. In contrast, glial cells such as myelinating oligodendrocytes are replenished from a pool of adult neural stem cells, termed oligodendrocyte precursor cells (OPCs). Therefore, our CNS has the ability to repair itself and remyelinate damaged axons.

Our researchers study the intrinsic mechanisms underlying this CNS regeneration. By understanding how remyelination occurs naturally in the brain and spinal cord, we aim to develop methods to enhance the efficiency of endogenous adult stem/precursor cell types to repair lesioned tissue.

Like all regenerative processes, however, remyelination progressively declines as we age. The mechanisms underlying this deterioration in myelin repair capacity are not fully understood. Therefore, a goal of this project is to understand this natural age-related decline in remyelination in order to find ways to promote the regenerative capacity of adult stem/precursor cells in the CNS.

Project findings and impact

The overall goal of this project is to identify and develop novel adjunct therapies for MS that could potentially prolong and improve quality of life for patients.

Research team

Dr Graham Sheridan

Dr Marcus Allen

Dr Greg Scutt

Output

Velasco, M & Sheridan, GK (2015) GLIA 63:E455-E456

Velasco, M & Sheridan, GK (2015) GLIA 63:E458-E458

Partners

Kumlesh Dev (Drug Development – Trinity College Dublin)

María Velasco (Drug Development – Trinity College Dublin)