Protein build-up may prevent repair in MS
22nd February, 2013
British and Dutch researchers have found that insoluble deposits of a protein, fibronectin, impair the re-growth of myelin in MS lesions.
The work, published in the journal Brain, suggests that strategies to prevent the accumulation of fibronectin in MS lesions could provide a new method to promote repair and regeneration of the nervous system in MS.
Myelin forms a protective sheath around nerve fibres and MS lesions result from a loss of myelin, which causes a blockage of electrical conduction along the nerves. Within MS lesions there is limited myelin repair that allows neurological symptoms to resolve, however, over time the capacity for remyelination is reduced, leaving nerve fibres vulnerable to permanent damage.
Fibronection, a protein that is usually involved in development of tissues and wound repair, is not found in healthy human brain tissue. However, previous studies of human MS brain tissue have shown that fibronectin is increased in MS brains and is particularly found in MS lesions.
The research team set out to investigate what role fibronection might play in the development of MS lesions.
First, using two different animal models of MS-like disease, the researchers showed that loss of myelin causes the surrounding support cells of the brain to produce fibronectin.
When there is no inflammation present the fibronectin is gradually cleared and the lesion remyelinates. In cases of chronic inflammation however, as seen in an inflammatory model of demyelination in mice and in human MS brain tissue, the fibronectin forms aggregates that remain in the lesion.
In the next phase of their research, the team showed that oligodendrocytes (myelin-producing cells of the brain) grown in the laboratory dish, are unable to regrow myelin in the presence of these fibronectin aggregates. Injecting fibronectin aggregates into the brains of mice also prevented the regrowth of myelin.
Taken together, the findings provide a strong case for a role for fibronectin aggregates in preventing repair in MS. The researchers suggest that strategies to promote remyelination in MS should include methods that prevent the accumulation of fibronectin.
The research opens a new avenue of enquiry in the search for better treatments and a cure for MS.
To read the abstract please click here