Methotrexate (MTX), a folate antagonist that blocks folic acid activity, is the most widely used disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis. It enters the cell via several pathways, one of which involves folate receptor β (FRβ), which is highly specific for cells present in the joints of patients with rheumatoid arthritis (RA). During the last two decades, a second generation of folate antagonists has been designed to address some of the limitations of MTX, which include adverse side effects and resistance. A new study examined the capacity of several of these new drugs to determine whether they could selectively target cells that express FRβ. The study was published in the January issue of Arthritis & Rheumatism (http://www3.interscience.wiley.com/journal/76509746/home).
Led by Gerrit Jansen of the VU University Medical Center in Amsterdam, researchers analyzed FRβ expression from biopsy samples from the knee joints of RA patients before and after four months of treatment with MTX and from controls. These experiments confirmed that FRβ expression is highly specific to activated macrophages (a type of immune cell that plays a role in the inflammatory response in RA) in the synovial membrane of RA patients.