New research could pave the way to safer treatments for arthritis

July 4, 2013

The increased risk of heart attack or stroke associated with many arthritis drugs may be avoidable, according to a new international study co-authored by researchers at Imperial College London.

Drugs such as Vioxx, diclofenac, ibuprofen and Celebrex operate by blocking an enzyme known as COX-2, whose presence in blood vessels has up until now been held responsible for these side effects. New research carried out on mice has revealed that COX-2 is largely absent from the major blood vessels and instead found in the brain, gut, and kidney as well as the gland in the chest.

Now that researchers know where in the body the drug is acting, they can begin to develop safer, more targeted drugs for patients with arthritis as well as cancer.

Arthritis drugs have long been associated with potentially fatal cardiovascular side-effects in patients. Health concerns led to the anti-inflammatory Vioxx being withdrawn from the market in 2004, and this week medical regulators have advised some patients to stop using the painkiller .

Researchers have always believed that COX-2 was found in the blood vessels where it was central to preventing the formation of clots. This meant that any drug that inhibited the enzyme was thought to lead to an increased risk of clotting.

The new study, published today in the journal PLOS ONE, reveals that COX-2 is largely absent from the major . Instead COX-2 appears to be present in the brain, kidney, thymus and gut, where it may well be affecting the .

Lead author, Professor Jane Mitchell of Imperial's Faculty of Medicine said: "Now we know the true sites of COX-2, we can begin to develop new ideas that will lead to better drugs for arthritis and cancer with fewer side effects."

The new research suggests future development of COX-2 inhibitors that carry reduced risk of stroke or may be possible. Professor Mitchell added: "This study does not provide all the answers, but once we understand exactly how COX-2 affects the cardiovascular system we will be in a position to design new therapies. This will not be easy but all the tools are available and we could be looking at new leads within five to ten years."

In order to accurately measure concentrations of COX-2 within the body, the researchers used mice whose COX-2 gene had been replaced with a gene called luciferase, which gives fireflies their distinctive glow. This allowed researchers to create detailed images of the distribution of COX-2 throughout the body.

Professor Anna Nicolaou, a co-author, now at the University of Manchester, said: "This study is the first to use such sophisticated techniques to determine the locations of COX-2 within the body. The use of mass spectrometry and genetically modified mice in this way represents a significant advance in the field."

This was echoed by Professor Tim Warner, a co-author from Queen Mary, University of London, who said: "These cutting edge techniques are at last supplying us with the definitive answers we need to understand the side effects of arthritis drugs. This could help improve therapy for many millions of patients worldwide."

Explore further: NSAIDs and cardiovascular risk explained

Related Stories

NSAIDs and cardiovascular risk explained

May 2, 2012
After nearly 13 years of study and intense debate, a pair of new papers from the Perelman School of Medicine, at the University of Pennsylvania have confirmed exactly how a once-popular class of anti-inflammatory drugs leads ...

Not taking gastroprotective drugs prescribed with anti-inflammatory medicines

April 16, 2012
To relieve pain, arthritis sufferers are prescribed medications that may include non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors, both of which can irritate the digestive tract. At times ...

Common painkillers linked to irregular heart rhythm: study

July 4, 2011
Commonly used painkillers to treat inflammation are linked to an increased risk of irregular heart rhythm (known as atrial fibrillation or flutter), concludes a study published in the British Medical Journal today.

Drugs without side effects: Researchers explore novel ways to classify proteins

April 26, 2013
Janelle Leuthaeuser is on the cutting edge of biophysics. A molecular genetics and genomics Ph.D. student, she is part of a nationwide effort to create a more efficient generation of protein-based drugs.

Recommended for you

Fluid in the knee holds clues for why osteoarthritis is more common in females

June 26, 2017
Researchers have more evidence that males and females are different, this time in the fluid that helps protect the cartilage in their knee joints.

Biologics before triple therapy not cost effective for rheumatoid arthritis

May 29, 2017
Stepping up to biologic therapy when methotrexate monotherapy fails offers minimal incremental benefit over using a combination of drugs known as triple therapy, yet incurs large costs for treating rheumatoid arthritis (RA). ...

Drug for refractory psoriatic arthritis shows promise in clinical trial

May 24, 2017
In a pivotal phase-3 clinical trial led by a Stanford University School of Medicine investigator, patients with psoriatic arthritis for whom standard-of-care pharmaceutical treatments have provided no lasting relief experienced ...

Cross-species links identified for osteoarthritis

May 17, 2017
New research from the University of Liverpool, published today in the journal npj Systems Biology and Applications, has identified 'cell messages' that could help identify the early stages of osteoarthritis (OA).

Osteoarthritis could be prevented with good diet and exercise

May 12, 2017
Osteoarthritis can potentially be prevented with a good diet and regular exercise, a new expert review published in the Nature Reviews Rheumatology reports.

Rodents with trouble walking reveal potential treatment approach for most common joint disease

May 11, 2017
Maintaining the supply of a molecule that helps to nourish cartilage prevented osteoarthritis in animal models of the disease, according to a report published in Nature Communications online May 11.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.