image: Dr. Jonathan Wall view more
Credit: UTHSC
Memphis, Tenn. (March 16, 2021) - The National Institute of Diabetes and Digestive and Kidney Diseases recently awarded Jonathan Wall, PhD, professor in the University of Tennessee Health Science Center's Graduate School of Medicine in Knoxville, a $1.79 million grant for his study titled "Developing a Theranostic Immunotherapy for Systemic Amyloidosis."
Amyloidosis is a rare disease that occurs when abnormal protein aggregates (called amyloid) build up in tissues and organs, interfering with their normal functioning. Since early stages of the disease are often asymptomatic, most patients only seek treatment once it is clinically advanced, at which time significant amyloid deposits exist in the tissues and organ damage is present. In most cases, a diagnosis of amyloidosis results from symptoms of cardiomyopathy, renal insufficiency, or peripheral neuropathy.
Current treatment focuses on limiting further production of amyloid protein in already diseased patients, but there is an urgent need to find a way to remove existing amyloid deposits.
Lab studies involving amyloid-binding antibodies or antibody fragments designed to recruit cells capable of clearing amyloid, have been successful, however, none have yet been approved for clinincal use. In this study, Dr. Wall and his team in the Amyloidosis and Cancer Theranostics Program in Knoxville aim to develop a new peptibody (a peptide-fused antibody fragment) capable of clearing amyloid deposits in tissue, that is also "readily labeled for imaging."
Dr. Wall has devoted 26 years to studying the pathogenesis of amyloid diseases. He and his team have conducted a Phase 1 FDA-approved PET/CT imaging trial involving a synthetic peptide capable of binding to amyloid and detecting the deposits in patients. In this new proposal, he will test how effective these novel peptibodies are at recruiting macrophages (cells that can recognize, engulf and destroy amyloid) and removing amyloid, using animal models of the disease. Their aim is to identify a lead candidate to use for molecular imaging and amyloid removal in clinical trials. "Our long-term goal is to generate an immunotherapeutic peptibody that can be radiolabeled to demonstrate amyloid binding in patients," Dr. Wall said. "The combination of identifying patients that would benefit from peptibody therapy, and an efficacious pan-amyloid reactive therapeutic could result in significant clinical benefit for patients with these devastating diseases."
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