A new drug called talarozole may help boost levels of retinoic acid in the body. Retinoic acid has been shown to suppress inflammation and joint cartilage damage caused by osteoarthritis.
- Osteoarthritis — a painful condition leading to joint pain, stiffness, and swelling — impacts 32 million US adults.
- Currently, treatments for hand osteoarthritis only manage and lessen symptoms.
- A new study has indicated that the drug talarozole can reduce and modify osteoarthritis symptoms.
- More research is being conducted to assess the medication’s potential in treating the condition.
There is currently no cure for OA, and effective treatment options are limited. However, a recent study published in Science Translational Medicine by a team at the University of Oxford in the UK discovered that levels of a particular molecule are low in individuals deemed at risk of developing the condition.
Researchers were able to test a potential new treatment for those affected by hand OA: a drug called talarozole.
Then, they collected samples of hand cartilage from 33 patients with hand OA undergoing surgery for the condition. Cells from these were analyzed alongside experimental models, and it was found that people at risk of hand OA had low levels of retinoic acid.
“ALDH1A2 is the key synthetic enzyme for the production of retinoic acid,” explained Dr. Tonia Vincent, professor of musculoskeletal biology and honorary rheumatologist of the University of Oxford and co-author of the study.
Vincent and her colleagues also saw an association between retinoic acid and inflammation — the latter of which is a symptom of OA in the joints.
“All-trans retinoic acid is a nutrient made in the body from vitamin A and helps cells grow and develop,” Rob Louie, a pharmacist and EVP of Clinical Services at RemedyOne, explained to Healthline.
But how does it influence inflammation?
“It appears to be a powerful anti-inflammatory mechanism that controls the acute response to tissue injury,” Vincent said.
Some inflammation in the body is good, particularly in helping repair muscles after stress or injury. But Vincent explained that it’s important for it to eventually ‘switch off’.
“Having low levels of retinoic acid presumably means that you are less able to switch off inflammation after injury, especially when this injury becomes chronic (like in osteoarthritis),” she stated.
According to Vincent, the research findings are unique.
“There is a small literature on retinoic acid as an anti-inflammatory signaling molecule,” she said. “But we are the first to demonstrate a clear mechanism for this and to show that it has a direct role in arthritis.”
Following their findings, the researchers tested a drug called talarozole on live mice and ex vivo pig joints with OA, to see if it had any effect on reducing inflammation.
“Talarozole is a retinoic acid metabolism blocking agent (RAMBA) that works by blocking the breakdown of all-trans retinoic acid, which results in an increase in their levels,” explained Louie.
The team at Oxford discovered that the drug successfully reduced inflammation in mice knee joints after just six hours. Furthermore, cartilage degradation and osteophyte formations (little bone spurs) were reduced after 26 days.
“We were surprised to see such a striking effect of talarozole on the bone shape change in OA,” admitted Vincent. This suggests “that retinoic acid is probably an important injury mechanism in several tissues.”
Talarozole was developed in the early 2000s, after which it underwent clinical testing for treating psoriasis and “had a brief license for a rare congenital condition of the skin,” said Vincent.
However, she stressed that it is currently not licensed or approved to treat any condition. So how did the researchers come about trialing it for OA treatment?
“We became aware of this class of drugs from the published literature and were looking for accessible agents that had been tested already in patients and which were predicted to increase retinoic acid levels,” Vincent revealed.
She continued: “We were lucky that such a drug already existed. This was an important consideration, as meaningful clinical translation is much faster if one can ‘repurpose’ an existing drug rather than develop one from scratch.”
OA is the most common form of arthritis, he noted, and “results from degeneration (wear and tear) of the cartilage that covers the end of the bones that form the joints.”
Once the cartilage has gone, the bones start to rub together — causing pain and inflammation.
According to Hardy, the most common symptoms of hand OA include:
- Bone spurs
There is currently no cure for OA.
“There is no proven method to replace the cartilage in a joint,” stated Hardy. As such, “treatment options are aimed at reducing the pain and inflammation resulting from arthritis.”
Louie explained that two types of medication are used to treat OA in the hands: topical and oral nonsteroidal anti-inflammatory drugs (NSAIDs).
“Topical NSAIDs would typically be the initial pharmacologic treatment, because they work well and are not associated with the adverse effects of the oral NSAIDs,” he revealed. “Oral NSAIDs are usually reserved for patients that don’t respond well to other therapies.”
Oral NSAIDs include medications such as ibuprofen, and Louie stated they should be used at the lowest dose and for the shortest time possible. This is because long-term use has the potential for gastrointestinal, cardiovascular, and renal side effects.
There are other options if NSAIDs prove ineffective, explained Hardy.
These include corticosteroid injections into the joints, “which serve to reduce the inflammation in the joint, thus reducing the pain,” he said. “Finally, there are various surgical options to address osteoarthritis, which usually involve joint replacements or joint fusions.”
Researchers have learned that a drug called talarozole could help reduce the adverse effects caused by low levels of retinoic acid in the body — which is linked to the development and symptoms of OA.
Currently, talarozole is undergoing additional clinical testing to establish its potential as a disease-modifying treatment for OA. This is notable, stated Hardy, as all current treatments are solely “aimed at managing and reducing the symptoms.”