A ray of hope for osteoarthritis patients

An existing chemical can stop the progression of osteoarthritis, a disease that physically impairs up to 50% of the elderly population aged 65 and above, according to the findings of a new study.

Bones have a soft tissue called cartilage at both their ends. This cartilage acts as a cushion, reducing friction between the bones and preventing them from rubbing against each other at the joints. Over the years, the cartilage undergoes wear and tear, and because the body is unable to repair it, this leads to movement difficulties in the old age.

In a developing human embryo, bones are formed with bony tissue replacing cartilage. The tissue ultimately replaces the cartilage entirely except at its ends. "The ends of our bones contain a special kind of cartilage called articular cartilage that remains in this form throughout our life, unless we develop osteoarthritis (OA)," explains Naibedya Chattopadhyay of the CSIR-Central Drug Research Institute, who was not associated with the study.

This is why X-ray of an osteoarthritis patient shows bone formation where cartilage should be present. "Here, the bone is forming on cartilage but at the wrong place and time," says Amitabha Bandyopadhyay, the study co-author and scientist at the Department of Biological Sciences and Bioengineering at the Indian Institute of Technology Kanpur.

Bandyopadhyay's group developed a mice line in which scientists can activate or deactivate a bone formation pathway – the Bone Morphogenetic Protein (BMP) signalling pathway – by injecting a chemical. The researchers found that mice developed osteoarthritis when this pathway was activated. They searched the literature for a chemical that inhibits the BMP signalling pathway and injected it into mice that had developed arthritis due to the activation of the pathway. They discovered that the inhibitor stopped the further progression of osteoarthritis in mice. The study was published in the journal Osteoarthritis and Cartilage (bit.ly/OA-study).

Currently, there is no drug available to treat osteoarthritis; treatment involves pain management with painkillers and non-steroidal anti-inflammatory drugs. Osteoarthritis patients have to undergo knee replacement surgery as a last resort. Bandyopadhyay says that if the drug is found to be safe and effective in human clinical trials, treating the disease in its early stages might prevent the need to operate.

Following the success of the inhibitor in treating osteoporosis induced in mice, Bandyopadhyay and colleagues want to test it on animals that naturally develop osteoarthritis, such as dogs. The team has secured funding for the trial. If the experiment in dogs shows the same efficacy as in mice and no side effects are found, says Bandyopadhyay, "we will immediately apply for it to be rolled out as veterinary medicine."

Considering the differences in joint anatomy, biomechanics, and disease progression between rodents and humans, remarks Chattopadhyay, dog or sheep models would provide a better understanding of the efficacy of the BMP inhibitor LDN-193189, before testing it in patients suffering from osteoarthritis.