Follow-up studies to develop drugs that could promote cartilage regeneration continue, but so far results haven’t been “as promising as we hoped,” he said.
Cell-based therapies have been studied in several clinical trials including one published in Nature Medicine that compared bone marrow aspirate, stromal cell fraction and mesenchymal stem cells to corticosteroid.2 Results revealed a response in the first few months but indicated no difference among the groups over the trial duration. Some trials are ongoing but so far these therapies “have not really panned out,” Dr. Loeser said.
Stopping Disease Progression Earlier
“With osteoarthritis, one of the issues is that we’re often seeing people that have more advanced disease,” he said, adding that clinical trials frequently enroll patients who have radiographic OA at grade two or grade three. “When we intervene at this stage, so far, other than things like exercise and weight loss, we really have not been that successful.
“The idea in the field is maybe we need to pick up people earlier, if we’re going to slow or stop disease progression before it gets too far,” he said. “Finding this pre-radiographic stage and finding the right group of people to intervene on are sort of the way people are thinking about for the future, and for that, we’re going to need better risk biomarkers.”
Biomarkers
To predict onset and progression of OA, researchers have studied biomarkers in blood, synovial fluid and imaging and investigated whether how a person walks or runs can identify abnormal gait mechanics that foreshadow development of the disease.
Cartilage acidic protein (CRTAC1) is one of several promising biomarkers identified through plasma proteomic studies, including one study of a biomarker panel that could possibly predict the onset of incident OA in advance of five to 10 years.3 “We’re getting to the point where we might have some prediction biomarkers,” he noted.
Some signs of progress have been seen, Dr. Loeser said. “Once we find the good biomarkers this might be really helpful for the future.”
Osteoarthritis has a variety of influences, such as genetics, environment, joint shape and multiple phenotypes, endotypes and therotypes, Dr. Loeser noted. That means investigating and developing effective therapies may require targeting OA subtypes instead of betting on the idea of one drug to suit all patients.
“Joint tissue destruction is mediated by a host of pro-inflammatory mediators and matrix degrading enzymes,” Dr. Loeser explained. “We don’t yet know (of) a master cytokine like TNF [tumor necrosis factor] that turned out to be so important in RA [rheumatoid arthritis] and so many other diseases…We haven’t found that yet, but it may be a host of things rather than a single cytokine.”
