Biogen identifies CNS repair molecule
molecule that may play a key role in the repair and regeneration of
the central nervous system (CNS). The finding could lead to
potential pathways for treating multiple sclerosis (MS) and other
demyelinating diseases.
MS is a chronic disease of the CNS in which the body's own immune cells break down myelin, a fatty substance that typically surrounds nerve cells like the insulation round a wire. Without myelin, nerves lose the ability to conduct electrical impulses and eventually die.
Current MS therapies can slow the progression of the disease, but none are able to repair the damage that the immune system inflicts on myelin. Although the CNS cells that typically wrap nerves in myelin are present in MS patients, they fail to restore the missing myelin sheath following an immune system attack.
Researchers reported that Biogen identified a molecular switch called LINGO-1 that appeared to control the ability of CNS cells to myelinate. The Biogen scientists discovered that LINGO-1 normally acts to prevent myelination and that the normal function of LINGO-1 could be blocked in laboratory tissue culture.
In experiments, researchers were able to induce CNS cells to generate large quantities of myelin by blocking LINGO-1 and, for the first time ever in a laboratory setting, to wrap it correctly around nerves.
"Although it is still uncertain whether we can transform these observations into a therapy, our research team has provided the first indications of a new pathway that may enable us to repair the nerve damage found in patients afflicted by MS and other serious demyelinating diseases," said Michael Gilman, Biogen Idec's executive vice president, research.
The sheer unpredictability of MS is the main factor that contributes to the economic costs of MS in terms of both lost productivity and direct and indirect healthcare expenses. Treating to delay disease progression can lesson this economic burden, as costs increase as the disease progresses.
The average cost per patient per year (1999 prices) in Germany was $29 727 (€34 169) with a cost to society of $3.57 billion (€4.10 billion). In the UK, the cost amounted to $26,935 (€30 960) per patient per year, with a total cost to society of $2.37 billion (€2.73 billion).
Biogen's research builds on papers recently published by its scientists on CNS nerve re-growth and regeneration. Earlier in 2005, Biogen researchers published a protein (TAJ/TROY) that acts as an important part of the receptor on CNS neurons that responds to growth-inhibitory molecules in myelin.
Specifically, these molecules prevent the re-growth of neurons following injury. Research on LINGO-1 and TAJ may also provide insight into how to potentially repair damage to the spinal cord.
"This work is of great interest to the field of myelin repair. It shows that there are, in the normal brain, certain factors that serve to exert a regulatory influence - and in the case of LINGO-1, a 'restraining' influence - on the myelination program," said David Colman, a principal investigator of the Myelin Repair Foundation and Wilder Penfield Professor and Director of the Montreal Neurological Institute and Hospital at McGill University.
As well as disease-modifying drugs, symptomatic drugs reduce the severity of symptoms but have no effect on the natural course of MS. The disease continues to progress.
Corticosteroids are used to reduce inflammation in the central nervous system during a relapse, and to speed up recovery from that relapse. However, corticosteroids have many side effects and do not slow down the progression of the disease, so they are not recommended for continuous use in MS.
Immunosuppressants, such as mitoxantrone, are sometimes used in MS to suppress the actions of the immune system in patients with rapidly worsening MS.
"We believe that the LINGO-1 research has significantly added to the body of knowledge about nerve repair in multiple sclerosis and other demyelinating diseases," said John Richert, vice president clinical and research programs at the National Multiple Sclerosis Society.
"We hope it will one day lead to improved treatments for MS and the repair of the central nervous system," he added.
The research is to be published in the June 2005 edition of Nature Neuroscience.
