Gene therapy for osteoarthritis in mice

An experimental gene therapy that protects cartilage from wear and deterioration has been shown to slow the development of osteoarthritis in mice.

Osteoarthritis is the most common form joint disease affecting over 8 million people in the UK. It is caused by the breakdown of cartilage, the slippery connective tissue between bones, due to age or injury. Without this protective layer, friction between the bones in joints causes the pain experienced by people with the condition.

Currently there is no cure for osteoarthritis, but a variety of treatments are available to manage the symptoms of the disease. For advanced cases, where physiotherapy and pain relief are ineffective, operations to replace the damaged joint with an artificial one can be performed. But the treatment is expensive — a hip replacement can cost the NHS) between £4

An experimental {GLINK(#:2317, gene therapy)} that protects cartilage from wear and deterioration has been shown to slow the development of osteoarthritis in mice.

Osteoarthritis is the most common form joint disease affecting over 8 million people in the UK. It is caused by the breakdown of cartilage, the slippery connective tissue between bones, due to age or injury. Without this protective layer, friction between the bones in joints causes the pain experienced by people with the condition.

Currently there is no cure for osteoarthritis, but a variety of treatments are available to manage the symptoms of the disease. For advanced cases, where physiotherapy and pain relief are ineffective, operations to replace the damaged joint with an artificial one can be performed. But the treatment is expensive — a hip replacement can cost the {GLINK(#:2447, NHS) between £4,000 and £7,000. Figures show the NHS carries out over 140,000 knee and hip replacements every year.

'As common as osteoarthritis may be, there's no therapy that significantly alters the course of the disease', said lead author of the study Merry Ruan, a PhD candidate at the Baylor College of Medicine (BCM) in Texas, USA. 'You can't just give somebody medication to fix the problem'.

In an effort to prevent cartilage deterioration, the researchers injected mice with a {GLINK(#:2316, gene)} called proteoglycan 4, which is known to produce a {GLINK(#:2331, protein)} that lubricates and protects bone and cartilage. A {GLINK(#:2345, virus)} was used to help deliver the gene throughout the affected area. The treatment stimulated {GLINK(#:2302, cells)} to produce extra levels of the protein, lubricin, which was seen to reinforce cartilage protection and significantly slow the development of osteoarthritis in mice.

'We found that gene therapy protects from osteoarthritis', said Brendan Lee, professor of molecular and human genetics at BCM and co-author of the study. 'Even if you delay joint replacement by 10 years you may have a big impact on quality of life as well as health care dollars'.

Gene therapy remains an experimental technique that works by replacing damaged genes, deactivating them or introducing new genes into the body. The technique is still associated with safety concerns over the possible development of tumours and the use of viral {GLINK(#:2432, vectors)} to introduce the therapy, however. The first gene therapy in Europe was approved by the European Medicines Agency only late last year, as reported in {LINK(#:93856, BioNews 680)}.

'You always have to worry that if you make too much of something you affect the skeleton', said Professor Lee. 'To the best of our knowledge, there didn't seem to be an adverse effect of making too much lubricin in the cartilage of these mice'.

The researchers say this therapeutic approach could be used to slow the progression of the disease in humans, or prevent it altogether. However, Professor Lee added: 'The weakest part is that in terms of the discovery we still don't think it would be enough to regenerate cartilage... For people who have late stage disease this therapy would not be sufficient'.

By 2014, researchers at the BCM hope to extend the animal study to horses, whose joints are more like humans.

Dr Brian Walit of Georgetown University Medical Centre, who was not involved in the study, cautioned that the results of the animal study may not be replicated in humans. 'Rat cartilage is not human cartilage, and rat joints are not human joints', he said.

The study was published in the journal Science Translational Medicine.