The drug talarozole, which raises retinoic acid levels, holds promise as a novel treatment for hand osteoarthritis.
According to Tonia Vincent, a Professor of Musculoskeletal Biology and Honorary Rheumatologist at Oxford’s NDORMS, hand osteoarthritis is a widespread and crippling ailment that disproportionately affects women, particularly during menopause. Despite its prevalence, there is currently a lack of effective treatments to address the condition.
The research team began by studying a prevalent gene variant associated with severe hand osteoarthritis (OA). By analyzing patient samples collected during routine hand surgery and conducting various experimental models, they discovered a crucial molecule, retinoic acid, that was deficient in individuals at high risk for the condition.
More than 40% of individuals will develop osteoarthritis (OA) during their lifetime. Hand (OA) is an extremely common form of OA and there are currently no disease-modifying treatments that effectively relieve symptoms or stop deformity and stiffness of the joints.
Professor Vincent added: “This project was only possible because of the multi-disciplinary approach that we took; working with our hand surgical colleagues, geneticists, data scientists, and biologists.”
As talarozole has an acceptable safety profile in human subjects, a small proof of concept clinical study is underway to see whether this drug might represent a new disease-modifying treatment in patients.
Dr. Neha Issar-Brown, Director of Research and Health Intelligence at the charity Versus Arthritis, which funded the research, said: ‘Around 8.5 million people in the UK live with OA. Despite often being dismissed as just a few aches and pains, OA can have a profound and far-reaching impact on life, affecting people’s ability to work, care for a family, or live independently.
‘There is an urgent need for disease-modifying treatments designed to prevent or reverse the painful symptoms of OA. This study reveals a new understanding of the causes of hand osteoarthritis, which could lead to identifying new biological targets for intervention in hand OA.
“This research is still at an early stage, but with these encouraging findings we are a big step closer to being able to develop a new class of disease-modifying drugs to treat osteoarthritis, prevent chronic pain, and enable people to live well with the condition,” Dr. Issar-Brown concludes.
Reference: “Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis” by Linyi Zhu, Pragash Kamalathevan, Lada A. Koneva, Jadwiga Miotla Zarebska, Anastasios Chanalaris, Heba Ismail, Akira Wiberg, Michael Ng, Hayat Muhammad, John Walsby-Tickle, James S.O. McCullagh, Fiona E. Watt, The Oxford Hand Surgical Team, Stephen N. Sansom, Dominic Furniss, Matthew D. Gardiner, Tonia L. Vincent, Nick Riley, Michelle Spiteri, Ian McNab, Christopher Little, Lucy Cogswell, Paul Critchley, Henk Giele and Rebecca Shirley, 21 December 2022, Science Translational Medicine.