Dagmar Kasper and Laszlo B Tankó look at developments in immunoassays.
Degenerative joint disease such as osteoarthritis (OA) and rheumatoid arthritis (RA) are major causes of disability and impaired quality of life among the elderly. Despite better understanding of the underlying pathomechanisms, current clinical practice for diagnosing these diseases mainly relies on symptom assessment, which has limited sensitivity and specificity.
By the time radiological techniques can reveal specific sign, the disease has advanced to a late phase with pronounced structural damage, when the only therapeutical option remaining is joint replacement. In the lack of established diagnostic methods allowing the detection of cartilage degradation, early diagnosis and disease monitoring remains a major challenge of health care professionals.
Immunoassays targeting different participants and end-products of cartilage degradation carry noteworthy potential for improving the methodology of research and clinical practice. There are three major categories of biological substances currently being investigated for their potential in preclinical, epidemiological, and clinical settings: constituents of the extra cellular matrix; proteolytic enzymes; and inflammatory markers.
In preclinical settings, biomarkers were shown to be able to:
* Differentiate animals with high or low cartilage turnover (Fig.1).
* Monitor disease progression under treatment with antiresorptive agents.
In epidemiologic/clinical studies undertaken in humans, biochemical markers were shown to be:
* Increased in patients with joint symptoms or manifest joint disease (Fig.2). u Able to predict the progression rate of degenerative joint disease.
* Able to point out individuals who will likely benefit from treatment.
Currently the clinical development of chondroprotective agents is considerably hampered by the poor sensitivity of radiological methods requiring many patients to be included in the trial and several years of treatment period to ensure sufficient statistical power.
Biomarkers might provide a more sensitive approach and can signal pharmacodynamic effects even after a few months of intervention.
Thus, they can be helpful in identifying the optimal dose range of candidate drugs in Phase I and II trials and thereby optimise Phase III assessments. The smaller number of patients and the shorter duration can ensure marketed drugs have affordable prices.
Dagmar Kasper is Head of S&M, Nordic Bioscience, Herlev, Denmark. www.nbdiagnostics.com. Laszlo B Tankó is Senior Research Physician, Center for Clinical and Basic Research, Ballerup, Denmark.
