Osteoarthritis (OA) is caused by the natural wear and tear of our joints. And when the cartilage between bones break down, there’s isn’t really anything we can do to restore that cushion to prevent pain, swelling, and stiff joints. In short, OA sufferers have very little options when it comes to treatment.
Here’s a bit of good news coming our way in 2020 though. According to Salk researchers, a combination of two experimental drugs could potentially reverse the cellular and molecular signs of OA. Results have only been observed so far in rats and in isolated human cartilage cells, however these discoveries could be groundbreaking for the study of arthritis.
“What’s really exciting is that this is potentially a therapy that can be translated to the clinic quite easily, We are excited to continue refining this promising combination therapy for human use.”
Juan Carlos Izpisua Belmonte, Salk Professor and Lead Author of the Study
Previous research revealed that two specific molecules, alpha-KLOTHO (αKLOTHO) and TGF beta receptor 2 (TGFβR2), could potentially be used to treat OA. αKLOTHO acts on the mesh of molecules surrounding articular cartilage cells, which in turn prevents the extra-cellular matrix from degrading. TGFβR2 acts more directly on cartilage cells, stimulating their proliferation and preventing their breakdown.
Individually, each drug was only shown to moderately curb OA in animal studies. But together, the drugs demonstrated better efficacy.
“From the very first time we tested this drug combination on just a few animals, we saw a huge improvement. We kept checking more animals and seeing the same encouraging results,” says Paloma Martinez-Redondo, a Salk research associate and first author of the new study.
Further experiments revealed 136 genes that were more active and 18 genes that were less active in the cartilage cells of treated rats compared to control rats. Among those were genes involved in inflammation and immune responses, suggesting some pathways by which the combination treatment works.
In an effort to test the drug combination’s applicability to humans, the team treated isolated human articular cartilage cells with results showing that levels of molecules involved in cell proliferation, extra-cellular matrix formation and cartilage cell identity all increased.
To be clear, these tests don’t mean that it will deliver the same results in actual humans, but researchers are looking at initial study results as a good sign that this drug combination could potentially work in OA patients.
Further research is required of course, to make sure that the drugs are safe to be taken directly and whether the combination of drugs could prevent the development of OA even before symptoms develop.
Their results were published in the journal Protein & Cell on January 16, 2020. Read more about the study here.