Overcoming Neurofibrosis in MS by Targeting Fibroblasts

Start Term
End Term
Funding Amount
$300,000
Affiliation(s)
University of Calgary
Geographic Region(s) / Province(s)
Alberta
Researcher(s)
Dr. Wee Yong
Research Priorities
Repair/Remyelination
Impact Goal(s)
Understand and Halt Disease Progression

Summary:

  • Multiple sclerosis (MS) causes loss of myelin and can result in damage to nerve fibres in the brain and spinal cord resulting in lesions. 
  • In animal models of MS, Dr. Wee Yong and team have found that there is an accumulation of specific cells called ‘fibroblasts’ in lesions, which may be preventing repair. In this study, the team aims to understand the role of fibroblasts in MS lesions and develop treatments that can target fibroblasts and promote repair. 
  • This research has the potential to uncover new strategies to promote repair of MS lesions.

Project Description: 
In MS, damage and loss of myelin, the protective covering of nerve fibres, results in lesions in the brain and spinal cord. These lesions have the capacity to naturally repair, but several factors may be hindering this process in people with MS. One such factor that may delay repair is the accumulation of a cell type called fibroblasts in MS lesions. In mouse models of MS, Dr. Wee Yong and team have found a higher number of fibroblasts in MS-like lesions and they appear to form a scar due to the presence of immune cells and lack of myelin-producing cells called oligodendrocytes. This scar-like feature is known as ‘neurofibrosis’.

In this study, the researchers aim to define the role of fibroblasts in MS lesions specifically in preventing myelin repair by oligodendrocytes. The team will also test whether anti-fibrotic therapeutics like pirfenidone can target the accumulation of fibroblasts in MS lesions. Pirfenidone is commonly used to treat severe fibrosis in the lung and was shown to improve MS symptoms in people with secondary progressive MS in a Phase 2 clinical trial. Dr. Yong and team will develop novel analogs of pirfenidone that can enter the central nervous system and overcome neurofibrosis to promote repair.

Potential Impact: This research will provide a better understanding of the factors that hinder repair processes in people living with MS and encourage the development of new therapeutics to enhance repair and remyelination. New therapies that can enhance repair and remyelination have the potential to delay disability progression and recover lost function in people with MS.

Project Status: In Progress