Supporting data from: Catalytic photooxygenation demonstrates therapeutic efficacy in transthyretin amyloidosis

The escalating global trend of aging populations has brought attention to
the rising prevalence of late-onset amyloid disorders. Among them, amyloid
transthyretin (ATTR) amyloidosis presents a growing area of unmet medical
needs. While current treatment modalities have demonstrated efficacy in
preventing or delaying amyloid generation, methodology to selectively
modify and neutralize existing amyloid burdens remains inadequately
addressed, leaving the fundamental irreversibility and hence the fatality
of these conditions a long-standing medical challenge. Here, we report the
first demonstration of therapeutic efficacy in ATTR amyloidosis via
dynamic control of ATTR aggregation and toxicity, enabled by
small-molecule organophotocatalysis. Selective incorporation of
hydrophilic oxygen atoms into the hydrophobic amyloid core reshapes the
aggregation landscape, neutralizing proteotoxicity and mitigating cellular
damage. Additionally, this targeted covalent modification significantly
reduces in vivo ROS levels, correlating with the observed therapeutic
effects in Caenorhabditis elegans, the only experimental model replicating
key clinical manifestations of the disease. Docking simulations elucidated
the molecular basis of catalyst performance, providing the foundational
blueprint for amyloid-neutralizing organophotocatalysis. Collectively,
this study provides a scalable approach to overcoming a persistent barrier
in amyloidosis therapy.