A worldwide genetic study of nearly 2 million people has led to the discovery of 700 genes that play a role in osteoarthritis. Ten percent of these code for proteins already “targeted” by existing drugs. This breakthrough offers new opportunities for therapies, including the reuse of drugs such as vitamin K and talarozole.
The discovery comes from a long-running, large-scale genome wide association study (GWAS) into the genes and DNA variations that play a role in the risk of developing osteoarthritis. It was conducted by the Genetics of Osteoarthritis consortium, which includes Erasmus MC.
Approved drugs
Remarkably, about ten percent of the genes found code for proteins already targeted by approved drugs. This opens the door to so-called “repurposing”: reusing existing drugs for a new indication, in this case osteoarthritis. According to Dr. Cindy Boer of Erasmus MC, a drug's chances of success double if there is genetic evidence of involvement in a relevant biological process.
The research, the results of which were published in the leading journal Nature, offers leads for more targeted and personalized treatment of osteoarthritis. "In one patient a certain biological pathway is active, in another a different one. By mapping these genetic differences, we can determine in the future who will benefit from which treatment," Boer said.
Vitamin K
A concrete example is the MGP gene, which is involved in the action of vitamin K in the joints. Boer will soon start a preclinical study in patients receiving knee replacements. The hope is that vitamin K, through its effect on preventing calcification, can slow the disease process. Another promising candidate is talarozole, a drug for acne and psoriasis, which is now being studied for effectiveness in hand osteoarthritis.
Although it may be years before these drugs become available to osteoarthritis patients, the genetic basis provides a solid foundation for future treatments. Given the expected increase in osteoarthritis worldwide - possibly 1 billion patients by 2050 - rapid progress in treatment is of great importance. Half of the Dutch over-60s are already struggling with osteoarthritis in at least one joint.
This research highlights the importance of biomedical research, as set out in Erasmus MC's Heading28 strategy. Understanding the biological mechanisms behind diseases is the key to innovation in healthcare. Earlier this year, it was also announced that researchers at Radboudumc have discovered a new technique that uses so-called “long reads” to find genetic causes of rare diseases.
