Scale up and Characterization of Immunoadsorbent Ligands

Northwestern University, Evanston IL

Investigators

Abstract

DESCRIPTION (provided by applicant): A serious complication of end stage renal failure is a debilitating disease called dialysis related amyloidosis (DRA). The pathogenesis of DRA, although not fully understood, is characterized by amyloid deposition in osteoarticular structures. The major protein component found in the amyloid depositions is beta2- microglobulin (b2m), which is found on most nucleated cells. Elevated levels of b2m are also associated with abnormal bone and synovial cell metabolism, which leads to an inflammatory response by cytokines. Elevated levels of b2-m have also been implicated in osteoarthritis-like changes in patients who are on long-term dialysis. Most of the current experimental approaches to remove elevated levels of b2m are inefficient since they are based on non-specific approaches such as size exclusion and hydrophobic interactions. Nonspecific removal of b2m also causes the loss of other blood proteins that may be important to the patient and complicates the elucidation of the disease process and assessment of new therapies. This proposal will focus on developing a blood detoxification system based on a single-chain antibody fragment (scFv) against b2m that can be effectively used to target b2m in the plasma of patients on long-term dialysis.