UK Human Functional Genomics Initiative: Musculoskeletal Cluster

Since the completion of the Human Genome Project two decades ago, we have entered a golden age of genetic discovery. Our understanding of how genetics determines how we look, how we think, and what diseases we get during our lives is increasingly comprehensive.

This golden age promised to revolutionise medicine, with new treatments for common diseases, but this promise has not yet been fully realised. In particular, very common diseases of the musculoskeletal system such as osteoarthritis and carpal tunnel syndrome, cause more years of disability and pain than any other disease class.

Our research will address this issue, using genetics to improve our understanding and treatment of these debilitating conditions.

The musculoskeletal system describes the bones, joints, cartilage, and soft tissues of the body that are responsible for movement. Diseases of the musculoskeletal system are responsible for extensive periods of reduced quality of life and physical limitations, but the amount of research into musculoskeletal disease does not reflect this importance, partly because of a lack of funding, and partly because historically it has been technically difficult to study musculoskeletal diseases.

In our study, we plan to overcome these hurdles by defining the genetic variations that predispose us to four very common, disabling, musculoskeletal conditions that have no current treatments beyond painkillers, physiotherapy, and surgery for severe disease (osteoarthritis, carpal tunnel syndrome, frozen shoulder, and Dupuytren's disease).

We will use waste tissue collected at surgery to look at the internal biology of the cells, and other molecules that make up the tissue (called the matrix), that are affected by the disease. We will then be able to link the genetic variations to changes in biological function. This will create a major resource that other musculoskeletal researchers around the world can use in their work. We will carefully interpret the results of these experiments to decide which genes and pathways are best suited as potential drug targets.

In the second part of our study, we will perform experiments on tissues in the lab to define the effects of interfering with these pathways on how the cells and tissues behave. We will also build special robotic "bioreactors" - robots to mimic the physical forces that these musculoskeletal tissues experience in the body. This will allow us to look at the interaction between disease genes and mechanical forces in the body.

We hope that the results of these analyses will provide enough evidence for us to begin human trials of new medicines in these diseases over the next five to ten years.

Our research team is made up of surgeons, medical doctors, genetics experts, biologists, lab scientists, and data specialists. With our combined expertise and experience, we hope to start human trials of new musculoskeletal disease treatments within the next five to ten years. We are uniquely suited to achieving the aims of this project, as we have previously achieved success in identifying a new treatment in hand osteoarthritis, that is currently undergoing clinical trials. This study will enable us to expand our research to several other conditions and finally begin to deliver on the promise of genetics to improve the health of the population.

We stand at the threshold of a significant leap in medical science. Our work, rooted in the intricate understanding of genetics, aspires to fulfil the long-standing promise of genetics - the promise to reshape the landscape of health and wellness. As we work deeper into this exciting endeavour, we are optimistic about translating our research into effective solutions that enhance public health and reduce the burden of musculoskeletal diseases.

The Musculoskeletal Cluster is embedded within NDORMS, Botnar Institute for Musculoskeletal Sciences, University of Oxford and it is led by Professor Dominic Furniss. The Musculoskeletal Cluster is part of a larger Functional Genomics Cluster (project led by Professor Jonathan Mill from the University of Exeter Medical School).

The project is funded by the Medical Research Council (MRC), in collaboration with the Biotechnology and Biological Sciences Research Council (BBSRC).