The University of Tennessee Graduate School of Medicine, Knoxville

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.

Dr. Towers's Research Affects Policy Change

The American Congress of Obstetricians and Gynecologists (ACOG) has updated its recommended therapy for pregnant women with an opioid-use disorder. The new guidance includes treatment options and screening recommendations pioneered by Craig Towers, MD, Professor of Obstetrics and Gynecology and a maternal-fetal medicine specialist.

On February 6, 2016, at the Society for Maternal-Fetal Medicine's annual meeting in Atlanta, Dr. Towers unveiled important research findings on a study he lead, showing evidence that maternal opiate detoxification during pregnancy significantly improves pregnancy outcome, without putting the fetus at risk.

Additionally, Dr. Towers's findings were published in some of the nation's leading obstetrics and gynecology publications and his work at the University of Tennessee Graduate School of Medicine has been profiled by national media outlets including CNN and Modern Healthcare magazine.

"As opiate addiction increasingly creeps into the pregnant population, mothers expose their unborn babies to drugs that often cause Neonatal Abstinence Syndrome (NAS)," said Dr. Towers. "Identifying opiate addicted pregnant women, getting them into a program that can first medically withdraw them and then be supported by follow-ups to further aid a drug-free lifestyle is of paramount importance."

According to ACOG, opioid agonist pharmacotherapy, also known as medication-assisted treatment (MAT), continues to be the recommended therapy for pregnant women with an opioid use disorder. However, this new guidance, spearheaded by Dr. Towers, also recognizes that medically supervised withdrawal can be considered under the care of a physician experienced in perinatal addiction treatment if a woman does not accept MAT.

"I am glad to hear ACOG is recognizing that medically supervised withdrawal under the care of an experienced physician can be offered to pregnant women with opioid use disorder as an additional option beyond MAT," said Dr. Towers. "This approach is very successful when connected with behavioral health and results in babies born who do not suffer NAS."