Osteoarthritis is the most common form of arthritis and affects millions of people worldwide.  With no known cure, osteoarthritis patients rely on lifestyle modifications and analgesics for relief of pain and inflammation to increase joint function. Unfortunately, these treatments do little to prevent further joint damage and surgical joint replacement may become necessary. Therefore, therapeutics that halt disease progression are the ultimate goal in drug development. Although osteoarthritis is not traditionally considered to be an immune mediated disease, activated macrophages have recently been found to play an important role in disease development and progression.  These activated macrophages are known to express folate receptor beta (FR�), which facilitates the receptor-targeted delivery of highly potent anti-inflammatory drugs specifically to sites of inflammation. In this study, EC0746, a folic acid-aminopterin conjugate, was evaluated for efficacy in a rat mono-iodoacetate (MIA) model of osteoarthritis.  MIA induced rats treated with EC0746 (500nmol/kg, SC, 3 times a week) were found to have decreased levels of activated macrophages in their joints when compared to nontreated osteoarthritis rats. Histological analysis of rats treated with EC0746 demonstrated a statistically significant reduction in joint damage, which was confirmed through radiographic analysis of the joints. Our findings indicate that treatment of osteoarthritis in rats with EC0746 has a considerable effect on slowing disease progression and preventing extensive joint damage.

Experimental osteoarthritis in rats is attenuated by EC0746, a folate receptor-targeted aminopterin conjugate

246th National Meeting (2013)

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