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NIH Supports Amyloidosis Research

Amyloidosis is a rare disease that people get when amyloid, a complex mix of protein fibers and sugars, builds up in the body's organs. When amyloidosis affects the whole body, it's called systemic. When it affects a certain organ, it's considered localized, as in patients with Alzheimer's disease. Light chain-associated amyloidosis (AL) is the most common form of systemic amyloid disease. There are about 4,500 new cases of AL each year in the United States. Systemic amyloid disease can damage almost any organ, including the kidneys, heart and nerves.

Jonathan Wall, PhD, is a professor at The University of Tennessee Graduate School of Medicine and the director of the Amyloidosis and Cancer Theranostics Program. He has been studying amyloidosis for over 20 years. He and his research team recently received a new three-year grant from the National Institutes of Health. The grant will allow them to study, "Pre-targeting Immunotherapy for Light Chain (AL) Amyloidosis."

For this project, Wall is working to develop a new two-stage therapy to treat patients with AL and any other forms of systemic amyloidosis. This therapy is designed to kick-start the body's immune system that can ultimately lead to the removal of amyloid from affected organs. This approach will build upon the success of current treatments for AL patients.

Wall said, "We hope this study will enhance the use of antibody therapy in patients with diverse forms of systemic amyloid disease. Our new approach to treating amyloid is a product of the work we have been doing for many years to generate new ways to image amyloid in patients."

This study will assess the use of a new bifunctional "peptope." A peptope is a combination of a amyloid-binding peptide that was previously developed by Wall's team, and a linear epitope sequence, that can activate the immune system.

"We have shown that peptopes attract antibodies to places where amyloid has been deposited. It signals the immune system to begin removing the amyloid," Wall said. "We anticipate that this two-stage immunotherapy will improve the effectiveness of current antibody treatments for AL patients. And it could potentially extend the use of antibodies to other forms of systemic amyloid disease."

There is no cure for AL yet, and the prognosis for patients is poor with a median survival of less than three years. This project will use technology that Wall and his team have worked with for years. The goal of the project is to take this new peptope and combine it with antibodies that are already approved for use in industry. Wall and his team hope that this approach will lead to a clinical trial of the peptope therapy in the future.

"Even though this project is early in development, we have already started conversations with stakeholders to maximize the success of this project," Wall said.

"Our lab is dedicated to translating research from the laboratory to the clinic. We do everything we can to create treatments, diagnostic tests and imaging agents that will benefit patients with amyloidosis."

This new approach will complement and extend current antibody-based therapies for amyloid removal. That can lead to improvement in organ function and increase patient's chances for long-term survival and remission.

Wall has been researching amyloidosis at the medical center since 1995. He has received continual funding to study the disease for almost 10 years. He currently has more than 10 patents related to his work.

The Graduate School of Medicine's research program has been working to improve outcomes for amyloidosis for over 50 years. The program develops new diagnostic techniques and drugs for this very rare disease.

Posted December 7, 2017