With advances in genetic sequencing techniques, computational tools and biobanks that are always growing larger, scientists are learning more about how small genetic changes can lead to an increased risk of disease. Investigators studying the causes of osteoarthritis have assessed genetic data from 77,000 osteoarthritis patients and revealed 52 new genetic variations that are connected to the disease. The work, including researchers at the Wellcome Sanger Institute and GSK (GlaxoSmithKline), has identified biological pathways that have not been linked to osteoarthritis before and may open up new avenues for treatment.
Osteoarthritis is a degenerative and painful condition impacting the joints. It’s different from rheumatoid arthritis, which is an autoimmune disorder. Osteoarthritis is a common problem that occurs as the cartilage that shields the ends of the bones wears down over time. Some medications can help relieve that pain of the disease, but, many patients have to have surgical joint replacements.
"Osteoarthritis is a very common, disabling disease with no cure. We have conducted the largest study of osteoarthritis to date and found over 50 new genetic changes that increase the risk of developing osteoarthritis. This is a major step forward in developing treatments to help the millions of people suffering from the disease,” said Professor Eleftheria Zeggini, who is now based at Helmholtz Zentrum München in Germany after previous work at the Wellcome Sanger Institute.
The researchers compared the genetic data from osteoarthritis patients with that of 370,000 healthy individuals, using the UK Biobank and a study called arcOGEN. The team assessed gene activity by looking at protein expression. They integrated genomic and proteomic data from tissue samples harvested from joint replacement surgery patients. This collection of datasets enabled the researchers to identify likely causal genes for osteoarthritis.
Ten of the genes they found, including cathepsin K (CTSK), transforming growth factor beta 1 (TGFB1), fibroblast growth factor 18 (FGF18), and interleukin 11 (IL11) are already targeted by existing drugs. One of those therapeutics is called INVOSSA - it treats knee osteoarthritis. Another is LCL-161, which is being developed as a breast cancer, leukemia, and myeloma treatment, may also be a useful new osteoarthritis drug.
"Osteoarthritis affects over 8.5 million people across the UK. We know that the condition impacts people in different ways, meaning the treatment that works for one person doesn't always work for someone else,” noted the Director of Research at Versus Arthritis Dr. Stephen Simpson.
"This study represents a hugely important milestone towards understanding the complexity of osteoarthritis and finding new treatments, and we are delighted that our support for the arcOGEN study has helped deliver this. In the long term, the research progresses us significantly on the journey to ending the pain, isolation, and fatigue of those living with arthritis."