Scientist Awarded $1.79M to Develop New Amyloidosis Treatment

Scientist Jonathan Wall, PhD, has won a $1.79-million grant to develop a potential treatment for amyloidosis, a group of conditions that includes familial amyloid polyneuropathy (FAP).

The grant, from the National Institute of Diabetes and Digestive and Kidney Diseases, will fund a research project, titled “Developing a Theranostic Immunotherapy for Systemic Amyloidosis,” in which Wall and his colleagues will attempt to develop a new therapeutic strategy for these disorders.

Amyloidosis is caused by the buildup of protein aggregates, known as amyloid, that interfere with normal cellular functioning. People with FAP often experience symptoms of polyneuropathy, or nerve damage resulting in numbness, tingling, and pain, due to the accumulation of these protein deposits in nerves.

The goal of current treatments for amyloidosis is to limit amyloid production, as a way of easing symptoms. However, a more curative approach is to find a way to remove the amyloid deposits already formed.

Some studies have investigated the therapeutic potential of using antibodies that are able to bind to amyloid deposits, or recruit immune cells to clear them, as a possible treatment for amyloidosis. Despite early signs of success, no such approach has yet reached the clinic.

In their new research project, Wall and his team at the University of Tennessee Health Science Center’s Graduate School of Medicine will attempt to create a peptibody, a molecule made up of a peptide (small protein) fused with an antibody, that can be labeled for detection in imaging tests and used to clear amyloid deposits from different tissues and organs.

“Our long-term goal is to generate an immunotherapeutic peptibody that can be radiolabeled to demonstrate amyloid binding in patients,” Wall, a professor at the Graduate School of Medicine in Knoxville, said in a press release.

While peptides have properties that make them attractive for therapeutic purposes, they tend to be rapidly cleared from the body. Resulting from the fusion of a peptide and an antibody, a peptibody combines the biological activity of a peptide with an antibody’s longer duration of activity. This makes peptibodies an attractive therapeutic alternative to conventional antibodies.

The researchers’ aim in this project is to develop a peptibody that is capable of promoting the clearance of amyloid deposits by recruiting macrophages — immune cells that are capable of digesting and destroying amyloid deposits — to specific tissues in animal models of disease.

Moreover, the new peptibody will be labeled with a radioactive imaging agent (radiotracer), so that it can be detected in positron emission tomography scans, signaling where these harmful amyloid deposits are within the body.

This project builds on previous work from Wall’s team, in which researchers were able to generate a lab-made peptide that was able to detect and bind to amyloid deposits in patients.

“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,” Wall said.