Breakthrough for Ankylosing Spondylitis
Posted by Danny Goldberg on Thu, Jul 21, 2011 @ 11:47 AM
Researchers at The University of Queensland Diamantina Institute (UQDI) in Australia have made a major breakthrough in the understanding of the molecular mechanisms underlying ankylosing spondylitis (AS), a form of arthritis that results in bone growth and can consequently cause the spine and or pelvis become fused into a fixed position.
Headed by Professor Matt Brown, UQDI scientists formed an international consortium with research groups in the UK, the U.S. and Canada to embark upon the largest study in history into the genetic causes of AS. Their research has identified eight new genes that help clarify previously unexplained aspects of AS. In particular, these genes help explain why bone formation occurs and why some AS patients also develop the conditions inflammatory bowel disease and/or psoriasis.
Professor Brown said the findings shed light on a 40-year-old genetic mystery. In the 1970s it was discovered that nearly all AS patients carried a particular gene called HLA-B27. Professor Brown said in the July 11, 2011 news release, “the link between AS and HLA-B27 is one of the strongest known genetic associations of any common disease. However, the precise role this gene plays in AS has never been clear until now.” He and his colleagues have discovered that a mutation in a second gene, ERAP1, only appears in HLA-B27 positive AS patients.
“These crucial findings provide the first confirmation that in humans, as has been shown in plant and other animal species, interaction between genes is important in influencing disease risk,” Professor Brown said. He also added ""We were surprised to see that, although HLA-B27 positive and negative AS cases were associated with the same genes, only HLA-B27 positive cases were associated with ERAP1. We then showed that the protective variants of ERAP1 reduced the risk of AS by producing less peptide for HLA-B27 to work with. This really narrows the possibilities down about how HLA-B27, which increases the risk of AS by about 80 times, operates to cause the disease."
He also commented to OTW, "We showed association with several new genes and AS, some of which are potential therapeutic targets. Following our previous finding that variants of IL23R are involved in AS, pharmaceutical trials of compounds targeting the IL23R pathway have commenced, and early results show that this is a very effective approach. This study identified other genes in the same pathway that are also involved in AS, strengthening the case for treatments targeting the pathway. Other potential therapeutic targets were also identified. A particularly interesting finding was that variation in the gene PTGER4, which encodes a receptor for prostaglandin E2, influences AS risk. This pathway is involved both in causing inflammation and in driving bone formation: AS is characterized by inflammation-induced bone formation. Therefore inhibiting this pathway may be effective in both reducing inflammation AND slowing the bony formation which causes most of the long term problems in this disease."
Reproduced from Orthopedics This Week
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