An old therapy for a variety of autoimmune diseases is to be made more efficient thanks to 10 years of research. The original treatment, intravenous immunoglobulin (IVIG), is an amalgam of specific antibodies made from the pooled blood plasma of thousands of healthy donors. It has been used on- and off-label in patients with lupus, arthritis, asthma and other immune disorders to varying degrees of success. New research conducted by Rockefeller University (NY, USA) shows that understanding how the therapy works at the molecular level can help create a new version that is much more potent.
Jeffrey Ravetch, Head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology at Rockefeller, has been studying the paradox of IVIG: immunoglobulin (Ig)G antibodies, which trigger autoimmune diseases, are what give IVIG its anti-inflammatory properties when pooled from healthy donors. After pinning down the molecular mechanism at the source of the contradiction — a single sugar molecule located at the very tip of some IgG antibodies — Ravetch and his collaborators produced an engineered IgG molecule that was 30 times more effective than IVIG alone when given to arthritic mice. "This paper provides a clear route for developing an alternative for IVIG, which could be of great benefit to patients with autoimmune diseases," says Ravetch. IVIg is also called IGIV as the pharma industry uses the term IGIV or Immune globulin Intra Venous.
The technology has been licensed to Centaurus Pharmaceuticals (MA, USA), which is working to develop a product that can be used in clinical trials. Ravetch is confident that the resulting drug could potentially provide relief for a variety of patients, especially for those where IVIG has little effect. In lupus, the current preparation has such low activity that the amount required to effect a noticeable difference exceeds the amount that can be realistically derived from the blood supply. However, according to Ravetch: "With the recombinant form you can make an unlimited, potent supply."
Centaurus is among several developers of antibody drugs in New England that have grabbed interest from big drug makers and venture funds. Monoclonal antibodies, cloned from antibodies that attack pathogens, are the fastest growing class of drugs on the global market, with $20 billion in annual sales and yearly revenue increases of 14 percent projected until 2012, according to Datamonitor PLC, a London pharmaceutical market research firm