Repurposed acne drug reverses hand osteoarthritis in animal models
Scientists investigating new treatments for hand osteoarthritis (OA) have made promising new inroads through research on a drug originally developed for acne and psoriasis. In animal models, the team was able to show that the drug can prevent progression of the disease, with work now underway in human patients to ascertain its potential as a new clinical therapy.
The research was carried out by scientists at the University of Oxford, who started by studying common variants in a gene called ALDH1A2 that had been linked to severe hand osteoarthritis (OA). The team confirmed this association by drawing on data from the UK Biobank study, and then acquired articular cartilage from 33 hand OA patients when they were undergoing surgery.
These samples were studied in combination with experimental models, which enabled the team to identify a certain molecule that was especially low in at-risk individuals. The molecule is called retinoic acid, and it is synthesized via the ALDH1A2 gene. Through RNA sequencing, the scientists were able to establish a reciprocal relationship between gene variants, lower retinoic acid and inflammation seen in OA.
Next, the scientists turned to a drug called talarozole developed to inhibit the metabolism of retinoic acid for the treatment of acne, psoriasis and related skin conditions. When used in knee joints of mouse models of OA, the drug was able to reduce cartilage injury and inflammation after six hours. The results were also replicated in ex vivo pig joints.
"This research is still at an early stage, but with these encouraging findings we are a big step closer in 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," said Dr. Neha Issar-Brown, Director of Research and Health Intelligence at the charity Versus Arthritis.
Because talarozole has an acceptable safety profile in humans, the scientists have high hopes for a smooth path to clinical use. They have undertaken another small proof of concept study to see whether these initial results can be replicated, and lay the foundation for a new treatment approach for hand OA.
"There is an urgent need for disease-modifying treatments designed to prevent or reverse the painful symptoms of OA,” said Issar-Brown. “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."
The research was published in the journal Science Translational Medicine.