Retinoic acid-boosting drug talarozole could be a promising new treatment for hand osteoarthritis.
Tonia Vincent, professor of musculoskeletal biology at the Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences (NDORMS) in Oxford, said: “Osteoarthritis of the hand is a common and debilitating medical condition that primarily affects women, particularly in the period of menopause. We currently do not have effective treatments that modify the disease.” Over 40% of individuals will develop osteoarthritis (OA) in their lifetime. Hand OA is an extremely common form of arthritis, and there are currently no disease-modifying treatments that effectively relieve symptoms or stop joint deformity and stiffness. Now, however, researchers have begun to study one common genetic variant that has been linked to a severe form of hand OA. Using patient samples collected during routine hand surgery, as well as a series of experimental models, they were able to identify a key molecule called retinoic acid, a metabolite involved in the functions of vitamin A (retinol) needed to growth and development , which has shown very particularly low profiles in subjects “at risk”. This study, therefore, reveals a new understanding of the causes of hand osteoarthritis, which could lead to the identification of new biological targets for treatment. Talarozole, a drug that has the power to increase retinoic acid would play a key role in the useful strategy to treat OA. In addition, it has an acceptable safety profile in humans, and a small clinical trial trial is underway to test whether this drug could represent a new disease-modifying treatment in patients.
Tonia Vincent added: ‘This project was only possible thanks to the multidisciplinary approach we took, working with our fellow hand surgeons, geneticists, data scientists and biologists.’ Dr Neha Issar-Brown, director of research and health intelligence at the Versus Arthritis charity, which funded the research, said: “Although often thought of as a simple ailment, OA can have a profound and far-reaching impact on life, affecting people’s ability to work, care for families or live independently. There is an urgent need for disease-modifying treatments designed to prevent or reverse the distressing symptoms of OA.
“With these encouraging results, we are one step closer to developing a new class of disease-modifying drugs to treat osteoarthritis, prevent chronic pain and enable people to live well with the condition,” the researchers conclude.