**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Name: Hirofumi Jono, Ph.D.
Institution: Department of Pharmacy, Kumamoto University Hospital,
Address: 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan

**Main Body of the Abstract**
Various types of amyloidosis pathologically proceed via production of amyloidogenic proteins by organs, formation of protein aggregates through structural changes, and their deposition on tissue. A growing body of evidence demonstrates that amyloidosis generally develops through 3 critical pathological steps: 1) production of amyloid precursor proteins, 2) amyloid formation, and 3) amyloid deposition. However, no clinically effective therapy independently showing therapeutic effects on all pathological step of amyloidosis is currently available. Here, we sought to develop a short hairpin RNA expression vector (shRNA) complex with cyclodextrin-appended cationic dendrimer (CDE), as a novel multi-target therapeutic drug that is capable of simultaneously suppressing these 3 pathological steps.
   In this study, we evaluated its therapeutic effects on systemic transthyretin (ATTR) amyloidosis and Alzheimer’s disease (AD) as localized amyloidosis, by targeting TTR and amyloid β, respectively. Our results clearly showed that, CDE/shRNA exhibited RNA interference effects to suppress amyloid protein production, and also achieved both inhibition of amyloid formation and disruption of existing amyloid fibrils, for TTR and amyloid β. The multi-target therapeutic effects of CDE/shRNA were further confirmed by evaluating TTR deposition reduction in early and late onset human ATTR amyloidosis model rats, and amyloid β deposition reduction in AppNL-G-F/NL-G-F AD model mice. Taken together, the CDE/shRNA complex exhibits multifunctional therapeutic efficacy, and may reveal novel strategies for establishing curative treatments for both systemic and localized amyloidosis.
(ACS Appl Mater Interfaces. 14, 40599-40611, 2022)



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Name: Hirofumi Jono, Ph.D.
Institution: Department of Pharmacy, Kumamoto University Hospital,
Address: 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan

**Main Body of the Abstract**
Various types of amyloidosis pathologically proceed via production of amyloidogenic proteins by organs, formation of protein aggregates through structural changes, and their deposition on tissue. A growing body of evidence demonstrates that amyloidosis generally develops through 3 critical pathological steps: 1) production of amyloid precursor proteins, 2) amyloid formation, and 3) amyloid deposition. However, no clinically effective therapy independently showing therapeutic effects on all pathological step of amyloidosis is currently available. Here, we sought to develop a short hairpin RNA expression vector (shRNA) complex with cyclodextrin-appended cationic dendrimer (CDE), as a novel multi-target therapeutic drug that is capable of simultaneously suppressing these 3 pathological steps.
   In this study, we evaluated its therapeutic effects on systemic transthyretin (ATTR) amyloidosis and Alzheimer’s disease (AD) as localized amyloidosis, by targeting TTR and amyloid β, respectively. Our results clearly showed that, CDE/shRNA exhibited RNA interference effects to suppress amyloid protein production, and also achieved both inhibition of amyloid formation and disruption of existing amyloid fibrils, for TTR and amyloid β. The multi-target therapeutic effects of CDE/shRNA were further confirmed by evaluating TTR deposition reduction in early and late onset human ATTR amyloidosis model rats, and amyloid β deposition reduction in _App^NL-G-F/NL-G-F^_ AD model mice. Taken together, the CDE/shRNA complex exhibits multifunctional therapeutic efficacy, and may reveal novel strategies for establishing curative treatments for both systemic and localized amyloidosis.
(_ACS Appl Mater Interfaces_. 14, 40599-40611, 2022)



Potential use of Multifunctional Therapeutic Cyclodextrin-Appended Dendrimer Complex for Systemic & Localized Amyloidosis Treatment PC146 (#199)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.