Research Project
2150212
DESCRIPTION: (Adapted from the applicant's abstract) The objective of this application is to produce a genetically engineered MAb appropriate for use as a therapeutic for diabetic nephropathy. The direct relationship between hyperglycemia and non-enzymatic glycation of proteins has implicated excess protein glycation as a cause of diabetic complications. There is convincing experimental evidence that glycated albumin adversely affects renal glomerular structure, function and metabolism; in ways analogous to diabetic nephropathy. Further, these effects are prevented by the A717 MAb which is specific for glycated albumin. Pre-clinical studies have shown that murine A717 is therapeutically efficacious in preventing diabetic nephropathy. However, murine antibodies elicit a brisk human anit-murine antibody response in patients, severly limiting their therapeutic usefulness. An attractive and viable strategy to improve therapeutic effectiveness is to produce a totally "humanized" version of A7l7. The resulting antibody is essentially human with the affinity and specificity of the original A7l7 antibody. Given the magnitude of the problem and the fact that there is no treatment to prevent diabetic nephropathy, this project is eminently justified.
