Two Enzymes Identified As Possible Drug Targets to Treat a Painful Form of Arthritis

Ankylosing spondylitis and two other debilitating conditions affect up to 3% of the global population. Researchers at the University of Queensland have initiated research involving important enzymes that activates the immune system.

For 40 years it was thought that ankylosing spondylitis carried a mutation on a gene called HLA-B27 and was the only gene involved in the development of the disease. But more than 26 other genes involved in the development of ankylosing spondylitis have been identified since 2007.

Professor Matt Brown, Director of Diamantina Institute and colleagues have studied how select enzymes work with HLA-B27 to help the immune system distinguish between what is self and what is foreign.

Their findings showed that in ankylosing spondylitis genetic variants result in the production of overactive enzymes that act in combination with HLA-B27 to induce arthritis.

University of Queensland Diamantina Institute Professor Brown said the agreement between UQ's commercialization arm, UniQuest, and Janssen Cilag Pty Limited (Janssen), would capitalize on more than a decade of research.

Ankylosing spondylitis, a painful form of arthritis is an incurable immune disease affecting the spine, joints and tendons, and can be difficult to diagnose.

"Patients often ignore the initial symptoms, including recurring back pain and stiffness, but if untreated it can slowly worsen and result in the spine becoming fused and totally inflexible," said Professor Brown.

Research published in Nature Communication last month shows that a specific enzyme works in conjunction with HLA-B27 and other genes associated with ankylosing spondylitis, psoriasis and inflammatory bowel disease.

Professor Brown said the culmination of this research led to the identification of two enzymes as promising drug targets.

He said, "We think that by inhibiting these enzymes we could be able to switch off the immune reaction that causes these common diseases. Our three-year collaboration seeks to capitalize on Janssen's drug discovery expertise including their capability to screen thousands of compounds to find inhibitors of the two enzymes, which we would optimize together."

Source: Medindia