Dublin-based scientists have made significant new discoveries about genes associated with multiple sclerosis, writes Cormac Sheridan
New genetic information about how multiple sclerosis develops and progresses has been announced by a team of researchers based at the Mater Hospital Dublin and University College Dublin. They reported important new findings last Friday at the 56th annual meeting of the American Academy of Neurology, being held this year in San Francisco.
Although the first clinical diagnosis of multiple sclerosis (MS) dates back to the mid-19th century, the precise cause of the degenerative illness has so far evaded discovery. It is now widely accepted that MS, which is particularly prevalent in Ireland and other parts of Northern Europe, has genetic and environmental components.
"Trying to define both of those has been very difficult over the years," says Dr Timothy Lynch, consultant neurologist at the Mater Hospital and a clinical investigator at UCD's Conway Institute for Biomolecular and Biomedical Sciences. "Disappointingly, no gene has been found to date."
Although some individuals are genetically predisposed to the disease, an external trigger - possibly a viral infection - is also thought to play a role. MS is characterised by regions of scarring on nerve tissue that occur through a process known as "demyelination".
Myelin is a fatty substance that normally sheaths the cells of the central nervous system (CNS). Protective myelin is broken down during a mis-directed attack by immune cells that somehow manage to cross the blood-brain barrier and infiltrate the CNS.
Myelin normally acts as an electrical insulator, ensuring that nerve impulses are propagated from one cell to the next. Its destruction leads to the loss of physical co-ordination that is characteristic of an MS flare-up.
The joint Mater-UCD team is led by Dr Lynch and Dr Peter Doran, co-ordinator of the genome resource unit of the Dublin Molecular Medicine Centre (a research partnership between UCD and Trinity College Dublin).
They first developed specialised software, used to interrogate public databases containing DNA data from MS patients and from healthy controls.
This "in silico" trawl helped the team discover a set of candidate DNA sequences, used in the hunt for genes whose expression was altered in tissue collected from MS patients in Ireland.
The team constructed a "biobank" containing samples of T-cells - immune cells centrally involved in initiating demyelination - that it obtained from 60 MS patients and from 20 healthy controls.
Their analysis of the biobank yielded 29 genes that exhibited altered expression patterns in MS patients. Five of these had a previously described association with MS, information that showed their research approach worked.
The apparent link between the other 24 genes and MS was new however, something that opens new lines of research. Whether their altered expression in MS contributes to or arises from the disease process is not yet clear, says Dorgan. "What we need to do now is to move towards defining the mechanisms of the disease."
Studying how gene expression alters in brain cells over time is part of this plan. The team also plans to take a broader snapshot of the genome of MS patients, both to confirm its initial findings and to widen the search for other genetic clues to the disease.
"What we are lining up at the moment - funding permitting - is to look at 10 patients from each group using the new Affymetrix gene chips," Dr Dorgan said.
These will allow the team to scan for hundreds of proteins at a time in their search for the genes directly linked to this difficult disease.