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ARM Innovation Hub
28 January, 2019 - 12:32 By Kate Sweeney

Sanger and GSK scientists map route for osteoarthritis cure

Gene genies from the Wellcome Sanger Institute in Cambridge, Big Pharma player GSK and collaborators have laid the foundations to discover a cure for osteoarthritis.

The breakthrough has emanated from the largest genetic study of osteoarthritis to date. The scientists uncovered 52 new genetic changes linked to the disease, which doubles the number of genetic regions associated with the disabling condition.

They analysed the genomes of over 77,000 people with osteoarthritis. Their findings, published in Nature Genetics, revealed new genes and biological pathways linked to osteoarthritis, which could help identify starting points for new medicines. 

Researchers also highlighted opportunities for existing medicines to be evaluated in osteoarthritis.

Almost 10 million people in the UK suffer from osteoarthritis, a degenerative joint disease in which a person’s joints become damaged, stop moving freely and become painful. There is no disease-modifying treatment for the disease. It is managed with pain relief medications and often culminates in joint replacement surgery, which has variable outcomes.

Osteoarthritis is the most prevalent musculoskeletal disease and a leading cause of disability worldwide. In the UK, the disease indirectly costs the economy £14.8 billion each year.

The collaborators analysed the whole genomes of over 77,000 people with osteoarthritis and over 370,000 healthy people using patient data from the UK Biobank resource and the arcOGEN study. The team studied many different types of osteoarthritis, including in knee and hip joints.

Professor Eleftheria Zeggini (pictured), previously from the Wellcome Sanger Institute and now based at Helmholtz Zentrum München in Germany, said: “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.”

In order to discover which genes cause osteoarthritis, the team incorporated additional functional genomic data and analysed gene activity by measuring gene expression down to the protein level. The team integrated genetic and proteomic data on tissue taken from patients undergoing joint replacement surgery.

By incorporating many different data sets, scientists were able to identify which genes were likely to be causal for osteoarthritis.

Ten of the genes were highlighted as targets of existing drugs, which are either in clinical development or approved for use against osteoarthritis and other diseases. These include the drugs INVOSSA, which is registered for knee osteoarthritis, and LCL-161, a drug in clinical development for the treatment of breast cancer, leukaemia and myeloma. The team suggest that the 10 drugs highlighted would be good candidates for testing in osteoarthritis.

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