New Drug Delivery System May Help Fight Rheumatoid Arthritis and Disease-Related Weight Loss

A potential method for treating rheumatoid arthritis, Crohn's disease and other chronic inflammatory disorders has been developed in an animal study conducted by Weizmann Institute and Ben-Gurion University researchers.

This approach -- described in the current issue of Cytokine -- may also be used to control excessive weight loss such as that occurring in cancer, AIDS and tuberculosis.

The method consists of a new delivery system that provides the organism with a steady supply of a natural therapeutic substance. It was developed by Prof. David Wallach of the Weizmann Institute together with Prof. Joseph Kost and graduate student Rom Eliaz of Ben-Gurion University of the Negev.

People with rheumatoid arthritis and other autoimmune disorders characterized by chronic inflammation produce increased amounts of tumor necrosis factor, or TNF. While TNF normally kills diseased cells and controls inflammation, it can sometimes get out of hand, causing a variety of illnesses. High levels of TNF are also responsible for excessive disease-related weight loss. Previous studies have shown that injecting soluble TNF receptors -- free-floating molecules that bind with TNF -- helps relieve the symptoms in human patients because the receptors absorb TNF.

But the benefits are short-lived, as these receptors are quickly cleared from the body. Attempts to keep them in the blood longer by modifying them prior to injection may fail because the organism is likely to perceive the modified molecules as foreign and develop antibodies against them. In their research on mice suffering from rheumatoid arthritis and/or excessive weight loss, Wallach and colleagues managed to maintain a steady level of natural TNF receptors in the blood, thereby imitating the process that normally occurs in the body when it tries to ward off the knockout punches of TNF.

They achieved this by developing a polymer delivery system that contains TNF receptors and continuously releases them in small amounts. Mice remained free of symptoms for several weeks after receiving injections of polymer-coated TNF receptors, while those that did not receive the injections developed joint swelling, impaired leg movement or lethal weight loss. In addition to being effective, this method is also economical because the costly TNF receptors are released gradually in very small amounts.

Prof. Wallach has studied TNF receptors for some 14 years and -- together with his Weizmann Institute colleagues -- was among the first researchers in the world to clone them. Wallach is a member of the Weizmann Institute's Department of Membrane Research and Biophysics; Kost and Eliaz are members of Ben-Gurion University's Department of Chemical Engineering.

This study was supported in part by Inter Lab, Nes Ziona, Israel; Ares Trading S.A., Switzerland, and Israel's Ministry of Science and the Arts.