From left to right: (Back row) Steve Kennel, Steve Foster, Jonathan Wall, Craig Wooliver and Trevor Hancock (Front Row) Tina Richey, Joseph Jackson, Emily Martin, Sallie Macy, Manasi Balachandran, Alan Stuckey and Angela Williams
The Amyloidosis and Cancer Theranostics research program at the University of Tennessee Graduate School of Medicine (GSM) led by Jonathan Wall, PhD, University Distinguished Professor and Assistant Dean of Research recently presented twelve abstracts of original research (five oral presentations and seven posters) at the 18th International Symposium on Amyloidosis (ISA) in Heidelberg, Germany. This year's symposium, which is held every two years, was the largest ever with over 1,100 attendees from around the world. The GSM research team received accolades at the symposium with their first-in-human studies of AT-01, a novel radioactive peptide for detecting diverse types of amyloidosis using PET/CT imaging.
Amyloidosis is a rare disease that is associated with the buildup of complex protein clumps or aggregates in the heart, kidneys, nerves, and other organs. Although over thirty amyloid-associated disorders have been identified, accurate diagnosis and effective treatment still face substantial obstacles. Patients typically see five different doctors before receiving a proper diagnosis because each patient may have a unique presentation of signs and symptoms, many of which tend to mimic those of other, more common, diseases. Current treatments for amyloidosis can slow the progress of the disease and therefore, the ability to image and detect the extent of amyloid may have significant implications for appropriate selection and timing of therapeutic interventions.
Four of the twelve abstracts presented by the GSM won awards at the symposium. Emily Martin, PhD, won the President's Award for Best Abstract by a Young Investigator for her oral presentation entitled Pan-amyloid reactivity of radioiodinated peptide 124I-AT-01 in patients with systemic amyloidosis demonstrated by PET /CT imaging. Joseph Jackson, PhD, also won the President's Award for his oral presentation entitled Collagen associated with AL amyloid inhibits fibril phagocytosis - Collagen degradation renders amyloid sensitive to uptake by the innate immune system. R. Eric Heidel, PhD and Steve Foster, MS both won Best Poster Awards for their presentations. All twelve abstracts presented at the symposium are listed below, along with links to view each one.
In addition to imaging amyloidosis, the Wall research team is investigating novel mechanisms to remove amyloid from affected organs, which current treatments do not appear to achieve. Currently, the AT-02, AT-04 and collaborative AT-03 studies focus on different reagents capable of removing amyloid deposits by engaging the patients' immune system. The AT-02 peptide-antibody complex is in the planning stages for first-in-human testing later this year. Dr. Wall stated, "Two of the biggest obstacles in finding ways to effectively treat amyloidosis are both early and accurate diagnosis, which we think can be achieved by first imaging the diverse types of amyloidosis and then removing amyloid deposits from affected organs."
The next International Symposium on Amyloidosis (ISA) will be held in Rochester, MN in June 2024, at the Mayo Clinic. "The ISA meeting is crucial," said Dr. Wall, "because it gives us the opportunity to get feedback on our research and to learn and exchange ideas with clinical and research experts that will hopefully propel us forward in the amyloid field."
Dr. Wall’s work is funded in part by grants from the National Institutes of Health and various industry partnerships.
(Left): Dr. Heidel accepting his award for Best Poster (Right): Dr. Wall giving his presentation on the AT-02 study
(Left): Dr. Jackson presenting his abstract at the symposium (Right): Dr. Martin receiving her President’s Award for Best Abstract by a Young Investigator
(Left): Dr. Balachandran giving her presentation at the symposium (Right): Dr. Heidel standing next to his poster
Title |
Presenter |
Preclinical characterization of AT-02, a pan-amyloid-binding immunoglobulin-peptide fusion protein capable of inducing enhanced phagocytosis of amyloid |
Jonathan Wall, PhD |
Results of the first-in-human PET/CT imaging study of the amyloid-reactive peptide 124I-AT-01 (124I-p5+14) for the detection of systemic amyloidosis |
Jonathan Wall, PhD |
Pan-amyloid reactivity of radioiodinated peptide 124I-AT-01 in patients with systemic amyloidosis demonstrated by PET /CT imaging |
Emily Martin, PhD |
Collagen associated with AL amyloid inhibits fibril phagocytosis - Collagen degradation renders amyloid sensitive to uptake by the innate immune system |
Joseph Jackson, PhD |
Development of novel human chimeric antigen receptor-macrophages (CAR-M) as a potential therapeutic for amyloid clearance |
Manasi Balachandran, PhD |
Differentiation of ATTR amyloidosis based on abdominothoracic organ-specific uptake of 124I-AT-01 (124I-p5+14} assessed by PET/CT imaging |
R. Eric Heidel, PhD |
Quantitative changes in organ-specific amyloid load in a patient with AL amyloidosis, measured by 124I-AT-01 PET/CT imaging, correlate with serum biomarkers |
Alan Stuckey BA, CNMT |
Detection of extracardiac amyloid in patients with ATTR amyloidosis by PET/CT imaging using the amyloidophilic radiotracer 124I-AT-01 (124I-p5+14) |
Jonathan Wall, PhD |
Preclinical characterization of AT-04, a pan-amyloid-binding Fc domain-peptide fusion, to serve as an opsonin for macrophage-mediated clearance of amyloid deposits |
J. Steve Foster, MS |
A kit method for direct radiolabeling the amyloid reactive peptide p5+14 with technetium-99m (99mTc) for the detection of cardiac amyloidosis by SPECT/CT imaging |
Stephen J. Kennel, PhD |
Assessing amyloid prevalence, type and extent of burden in the ligamentum flavum of patients with spinal stenosis undergoing routine laminectomy |
Emily Martin, PhD |
AT-03 demonstrated pan-amyloid binding and stimulated the removal of amyloid deposits through macrophage-mediated phagocytosis |
Christophe Sirac, PhD - Collaborator in Limoges, France |
Link to Presentations: https://gsm.utmck.edu/research/ACTP/isa2022.cfm
Posted: September 29, 2022
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