MS Society-funded research aims at helping repair nerves damaged by MS
Background: What do we know about repair in MS?
The majority of therapies for MS specifically target components of the immune system that are believed to cause damage to tissues in the brain and spinal cord. Although these ‘immunomodulatory’ treatments are successful in reducing myelin injury, they are unable to repair or regrow myelin that has already been stripped away from nerve cells. The absence of myelin repair can lead to further deterioration of the exposed nerve cells, which is often the first step towards progressive MS.
Two new publications add to understanding remyelination
Research into how myelin can be repaired following an attack in MS, a process termed remyelination, is gaining momentum. Two recently published MS Society-funded studies show headway in the effort to understand remyelination and the key cellular players involved.
One study comes from the Medical Research Council Centre for Regenerative Medicine at the University of Edinburgh. First author Dr. Veronique Miron is a MS Society Postdoctoral Fellowship awardee whose research is focused on myelin repair. The study, published in Nature Neuroscience, reveals an association between MS and a group of cells called macrophages. Important members of the immune system, macrophages have the ability to recognize foreign invaders and signal the white blood cells to find and kill the invaders. Recent evidence suggests that macrophages may play a role in promoting inflammation which exacerbates MS disease. Interestingly, other studies demonstrate that macrophages are also capable of boosting regrowth of myelin. Dr. Miron and colleagues are trying to better understand the two-sided role of macrophages in MS.
The second study looks at remyelination from a different angle. Doctoral Studentship recipients Ryan O’Meara and John-Paul Michalski, who work under MS Society-funded senior research Dr. Rashmi Kothary at the Ottawa Hospital Research Institute, published an article in The Journal of Neuroscience which breaks down the mechanism of oligodendrocyte development. This information is critical to understanding the capacity for myelin repair in MS as oligodendrocytes are the cells which produce myelin. In the article, researchers identify the unique role of integrin-linked kinase (ILK), which is a protein essential for oligodendrocyte development and hence myelin production.
Study methods and results:
The study by Dr. Miron and colleagues incorporated a series of advanced animal and cell experiments allowing the researchers to observe, in detail, how macrophages influence MS disease. They discovered that macrophages can transform into a specific macrophage subtype which promotes repair of myelin. They also discovered that following loss of or damage to myelin, macrophages release a compound called activin-A, which activates production of more myelin.Also using animal and cell experiments, O’Meara and colleagues tested the role of ILK in oligodendrocyte development and ability to produce myelin. Data revealed that loss of ILK disrupts the formation of oligodendrocytes and their capacity to produce myelin around nerves. The researchers took the study one step further by determining the mechanisms that are affected by loss of ILK, thus identifying important pathways by which oligodendrocytes produce myelin.
Studies in basic science at the most detailed biological level are imperative in understanding MS. Information from such studies paves the way for the development of treatments that will stop MS in its tracks and lead to improved health. Much work has been done to date to understand the autoimmune nature of MS, but treatments that are designed to curb the effects of immune cells are only partially effective.
“Approved therapies for multiple sclerosis work by reducing the initial myelin injury – they do not promote myelin regeneration. This study could help find new drug targets to enhance myelin regeneration and help to restore lost function in patients with multiple sclerosis.” – Dr. Miron
Decoding the complex process of myelin repair can result in significant changes in the way we treat MS. First, it will help in the development of a new class of therapies designed to enhance the repair process. Such therapies would result in less disruption of communication between neurons in the brain and improved function in the body Second, therapies focused on repair will slow down or halt progression of disability, preventing individuals with MS from entering the progressive stage of the disease. Overall, these two recently published MS Society-funded studies reveal new biological components that, when targeted therapeutically, could potentially rebuild the myelin that has been lost in MS.
“In order to address the goal of remyelination, we must understand
how myelination occurs in the first place. Our study has identified
ILK as a mediator of myelination, and this knowledge will be useful
when considering therapeutic avenues aimed at promoting
– Ryan O’Meara
Miron, VE et al. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nature Neuroscience 2013 July 21 [Epub ahead of print]
O’Meara, RW et al. Integrin-linked kinase regulates process extension in oligodendrocytes via control of actin cytoskeletal dynamics. The Journal of Neuroscience 2013; 33(23):9781-93