Osteoarthritis is a painful and debilitating condition that affects hundreds of millions of people. The condition significantly affects a patient’s mobility, sleep, and ability to work, ultimately impacting their quality of life and mental health. Treatments involve exercise or medication to reduce pain, but they don’t target underlying structural problems in the joints. Additionally, these treatments do not slow or stop the progression of the disease, and may have serious side-effects on organs such as the liver, kidneys or heart. The search for a treatment that can reduce osteoarthritis pain and treat the affected joint structures remains a ‘substantial unmet medical need’. Read More
Recently, researchers uncovered a genetic susceptibility to osteoarthritis associated with a protein called GDF5, which is involved in skeletal development. This protein is responsible for joint cartilage formation in the embryo. If it is under-expressed in adulthood, individuals are more likely to develop osteoarthritis. In fact, studies have revealed that supplementation with GDF5 could be a beneficial treatment for osteoarthritis. With GDF5, however, there is a risk of unwanted side-effects on bone formation.
Dr Kerstin Kleinschmidt-Doerr at Merck Healthcare and colleagues have built on this research, by exploring a modified form of the GDF5 protein, called R399E. The researchers first tested the effects of R399E on joint tissue samples from osteoarthritis patients. The protein showed promising positive effects in these samples, including reducing inflammation and increasing the concentrations of molecules that indicate cartilage growth.
The team then tested their new protein in rabbits with osteoarthritis in one knee. After one injection into the rabbit knees, the team measured high concentrations of R399E for up to one month. Based on their data, the team drew the conclusion that three injections over a six-month period might result in measurable improvements in the joints of human patients.
To assess whether the rabbits experienced pain relief from the treatment, the researchers measured how much weight the animals voluntarily placed on their arthritic leg. This is a special feature of the study that the researchers are particularly proud of. These measurements of comparatively weak knee pain, which were independent of observers, were only possible and meaningful because the animals were treated with particular care and low stress throughout the study.
Remarkably, there was a significant reduction in pain symptoms in the rabbits just six hours after treatment, likely due to anti-inflammatory effects. The pain reduction observed was as good or greater than that provided by analgesic drugs that effectively reduce osteoarthritis pain in human patients. Upon examining the joint tissues after 13 weeks, the researchers found that structural damage was significantly less in the treated rabbit knees compared to those in the placebo-treated control group.
Dr Kleinschmidt-Doerr and her colleagues then confirmed the pain-relieving and tissue-protecting effects of R399E in sheep with osteoarthritis.
The team’s experiments with sheep, rabbits and human tissue samples clearly demonstrate the potential of R399E in both reducing pain and improving joint structures in osteoarthritis. Based on these data, it seems justified to next test the efficacy of R399E in human patients in a clinical trial. With over 300 million people suffering from osteoarthritis worldwide, the impact of such a treatment on global health and wellbeing would be revolutionary.
