The announcement of two new genes
implicated in the degenerative bone disease ankylosing
spondylitis (AS) came with an added bonus: a drug for
Crohn's disease that suppresses one of these same genes
is currently in development. The findings, from an international
collaboration of arthritis researchers, appear in the
October 21 issue of Nature Genetics.
AS, a disabling form of arthritis,
afflicts as many as 300,000 Canadians and is three times
more common in men. It's notoriously underdiagnosed,
especially when it appears in childhood. The chronic
inflammation of the spinal joints gets worse over time,
causing stiffness and pain in the back. In severe cases,
the spinal joints eventually fuse together and patients
become unable to straighten or bend. There's no cure
for it and drugs, such as NSAIDs and corticosteroids,
only offer temporary relief.
ALL
IN THE FAMILY
It's recently become apparent that families at elevated
risk of inflammatory bowel disease are also at higher
risk of AS. The genetic locus IL-23R plays a large role
in inflammatory bowel disease, and sure enough IL-23R
is one of the two loci identified by the new research
as key in AS. The other is called ARTS1, a gene that
has cropped up before in studies of blood pressure regulation
and tumour suppression.
A third gene, HLA-B27, has been
known for nearly 40 years to be involved in AS, but
no one knew why it was failing to regulate its protein
properly. It now appears that the fault lies with ARTS1,
which provides faulty information to the HLA-B27 protein.
A person born with all three disease genes would have
a one in four chance of developing AS.
"We've long known that the HLA-B27
gene accounts for 40% of the overall cause of AS," said
Dr John Reveille of the University Texas Medical School
at Houston, one of the researchers. "Now we have found
two new genes. Together with HLA-B27, these genes account
for roughly 70% of the overall cause. That means we've
almost nailed this disease. Within the next year, I
predict we will have identified all the genes that play
a role in this insidious disease. There is more exciting
news to come."
TREATMENT
ALMOST AT HAND
We've heard that before in genetic research, of course,
but this time there's a difference. A treatment for
Crohn's disease that suppresses IL-23R is already in
human trials, and there's every reason to suspect that,
if proved safe, it could also have a beneficial effect
in AS. The timing is good, because early hopes that
anti-tumour necrosis factor meds, which block part of
the autoimmune response involved in AS, might stop this
disease have been fading lately.
For the Wellcome Trust, which is
a member of the consortium looking into AS, this is
just part of a far larger project to determine the multiple
genetic causes of autoimmune disease. Genetic research
hit a wall about 10 years ago, when it quickly became
apparent that only a few diseases, such as cystic fibrosis,
had single genetic causes. Most came from a combination
of gene variants, acting in conjunction with some unknown
environmental trigger.
It is these complex diseases that
Wellcome is now attacking, and their success stems from
painstaking research into family disease histories,
which has enabled them to see how one autoimmune disease
appears to increase the risk of another. They expect
to produce further results this year that may unlock
genetic secrets of thyroid disease, multiple sclerosis
and even breast cancer.
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