Study reveals new genes and biological pathways related to osteoarthritis

In the largest genetic study on osteoarthritis, an international team of scientists, including researchers from the University of Sheffield, discovered 52 new genetic changes linked to the disease, doubling the number of genetic regions badociated with the disease. disabling.

Scientists at GSK's Wellcome Sanger Institute and their collaborators – including Mark Wilkinson, professor of orthopedics at the University of Sheffield – have badyzed the genomes of more than 77,000 people with osteoarthritis.

Their findings, published today (January 21, 2019) in the journal Nature Genetics, revealed new genes and biological pathways related to osteoarthritis, which could help identify the starting points of new drugs. The researchers also highlighted the possibilities of evaluation of existing drugs in the treatment of osteoarthritis.

In the UK, nearly ten million people suffer from osteoarthritis, a degenerative joint disease in which a person's joints are damaged, stop moving freely and become painful. There is no basic treatment for osteoarthritis. The disease is managed with pain medication and often results in joint replacement surgery, the results of which vary.

Professor Wilkinson of the Department of Oncology and Metabolism and Honorary Consultant in Orthopedic Surgery at Sheffield University Hospitals, NHS Foundation Trust, said: "Osteoarthritis is the leading cause of chronic disability in the This study represents the largest genetic epidemiological study to date in our attempts to understand what makes a person more likely to develop the disease than another.

"In addition to examining the inherited factors that underlie susceptibility to disease, we also examined how genes bind to form pathways that underlie the biology of the disease.

"This helps us to identify the key points on which we could target the development of new treatments for the disease.We show here data to support the reuse of existing treatments, some drugs under development and new avenues for the development of new treatments for the disease. 39, drug exploration. "

Professor Wilkinson added, "The only treatment we currently have to treat persistent symptomatic osteoarthritis is the replacement of the joint.With the work presented here, we are advancing science towards our goal of improving the quality of life. improve the lives of patients with osteoarthritis. "

Osteoarthritis is the most common musculoskeletal disease and one of the leading causes of disability in the world. In the UK, the disease indirectly costs the economy £ 14.8 billion annually *.

To discover the genetics underlying Osteoarthritis, scientists from the Sanger Institute, GSK and their collaborators badyzed the entire genome of more than 77,000 people with osteoarthritis and more 370,000 healthy people using data from the British Biobank database and the arcOGEN ** study.
The team has studied many types of osteoarthritis, especially at the knee and hip joints.

Professor Eleftheria Zeggini, formerly of the Wellcome Sanger Institute and now based at the Helmholtz Zentrum München in Germany, said: "Osteoarthritis is a widespread disabling disease without curative treatment, new genetic changes that increase risk. to develop osteoarthritis.This is a major step forward in the development of treatments to help millions of people suffering from the disease. "

In order to uncover the genes responsible for osteoarthritis, the team incorporated additional functional genomic data and badyzed gene activity by measuring gene expression up to the level of osteoarthritis. the protein. The team has integrated genetic and proteomic data into tissues collected from patients undergoing joint replacement surgery. By incorporating many different datasets, scientists have been able to identify genes that may be causing osteoarthritis.

Ten of the genes have been highlighted as targets of existing drugs, under clinical development or approved for use in the treatment of osteoarthritis and other diseases. These include the INVOSSA drugs, which are registered for knee osteoarthritis, and LCL-161, a drug in clinical development for the treatment of bad cancer, leukemia and myeloma. The team suggested that the ten drugs highlighted would be good candidates for screening tests for osteoarthritis.

Dr. Stephen Simpson, director of research at Versus Arthritis, who supported the arcOGEN study, said: "Osteoarthritis affects more than 8.5 million people across the UK. that the disease affects people in different ways, that is, the treatment that works for one person does not always work for someone else.

"This study represents an extremely important step towards understanding the complexity of osteoarthritis and the discovery of new treatments, and we are delighted that our support for the arcOGEN study has achieved this goal. , research significantly advances the pain, isolation and fatigue of people with arthritis. "