Structural Basis for Monoclonal Antibody Therapy for Transthyretin Amyloidosis

The disease of transthyretin (TTR) amyloidosis (ATTR) has been known since the 1960s, and during the past 60 or so years, there has been a sustained period of steady discoveries that have led to the current model of ATTR pathogenesis. More recent research has achieved major advances in both diagnost...

Full description

Saved in:
Bibliographic Details
Main Author: Avi Chakrabartty
Format: Article
Language:English
Published: MDPI AG 2024-09-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/17/9/1225
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850259813183782912
author Avi Chakrabartty
author_facet Avi Chakrabartty
author_sort Avi Chakrabartty
collection DOAJ
description The disease of transthyretin (TTR) amyloidosis (ATTR) has been known since the 1960s, and during the past 60 or so years, there has been a sustained period of steady discoveries that have led to the current model of ATTR pathogenesis. More recent research has achieved major advances in both diagnostics and therapeutics for ATTR, which are having a significant impact on ATTR patients today. Aiding these recent achievements has been the remarkable ability of cryo-electron microscopy (EM) to determine high-resolution structures of amyloid fibrils obtained from individual patients. Here, we will examine the cryo-EM structures of transthyretin amyloid fibrils to explore the structural basis of the two monoclonal antibody therapies for ATTR that are in clinical trials, ALXN-2220 and Coramitug, as well as to point out potential applications of this approach to other systemic amyloid diseases.
format Article
id doaj-art-e71e0c31f22f4dd09cdecf9ea4c32fd1
institution OA Journals
issn 1424-8247
language English
publishDate 2024-09-01
publisher MDPI AG
record_format Article
series Pharmaceuticals
spelling doaj-art-e71e0c31f22f4dd09cdecf9ea4c32fd12025-08-20T01:55:46ZengMDPI AGPharmaceuticals1424-82472024-09-01179122510.3390/ph17091225Structural Basis for Monoclonal Antibody Therapy for Transthyretin AmyloidosisAvi Chakrabartty0Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 2M9, CanadaThe disease of transthyretin (TTR) amyloidosis (ATTR) has been known since the 1960s, and during the past 60 or so years, there has been a sustained period of steady discoveries that have led to the current model of ATTR pathogenesis. More recent research has achieved major advances in both diagnostics and therapeutics for ATTR, which are having a significant impact on ATTR patients today. Aiding these recent achievements has been the remarkable ability of cryo-electron microscopy (EM) to determine high-resolution structures of amyloid fibrils obtained from individual patients. Here, we will examine the cryo-EM structures of transthyretin amyloid fibrils to explore the structural basis of the two monoclonal antibody therapies for ATTR that are in clinical trials, ALXN-2220 and Coramitug, as well as to point out potential applications of this approach to other systemic amyloid diseases.https://www.mdpi.com/1424-8247/17/9/1225transthyretinamyloidosisantibody therapyprotein structurecryo-electron microscopy
spellingShingle Avi Chakrabartty
Structural Basis for Monoclonal Antibody Therapy for Transthyretin Amyloidosis
Pharmaceuticals
transthyretin
amyloidosis
antibody therapy
protein structure
cryo-electron microscopy
title Structural Basis for Monoclonal Antibody Therapy for Transthyretin Amyloidosis
title_full Structural Basis for Monoclonal Antibody Therapy for Transthyretin Amyloidosis
title_fullStr Structural Basis for Monoclonal Antibody Therapy for Transthyretin Amyloidosis
title_full_unstemmed Structural Basis for Monoclonal Antibody Therapy for Transthyretin Amyloidosis
title_short Structural Basis for Monoclonal Antibody Therapy for Transthyretin Amyloidosis
title_sort structural basis for monoclonal antibody therapy for transthyretin amyloidosis
topic transthyretin
amyloidosis
antibody therapy
protein structure
cryo-electron microscopy
url https://www.mdpi.com/1424-8247/17/9/1225
work_keys_str_mv AT avichakrabartty structuralbasisformonoclonalantibodytherapyfortransthyretinamyloidosis