Towards Optimal Control of Amyloid Fibrillation

TL;DR

This paper applies optimal control theory to determine the best dosing strategy for amyloid inhibitors like EGCG, balancing effectiveness and toxicity, supported by analytical solutions and experimental validation.

Contribution

It introduces an optimal control framework for amyloid fibrillation inhibition, providing analytical solutions and systematic comparisons with traditional dosing strategies.

Findings

Optimal control trajectories improve inhibitor efficacy.

Model parameters significantly influence dosing strategies.

Validated strategies outperform traditional approaches.

Abstract

EGCG, as a representative of amyloid inhibitors, has shown a promising ability against Abeta fibrillation by directly degradating the mature fibrils. Most previous studies have been focusing on its functional mechanisms, meanwhile its optimal dosage has been seldom considered. To solve this critical issue, we refer to the generalized Logistics model for amyloid fibrillation and inhibition and adopt the optimal control theory to balance the effectiveness and cost (or toxicity) of inhibitors. The optimal control trajectory of inhibitors is analytically solved, based on which the influence of model parameters, the difference between the optimal control strategy and several traditional drug dosing strategies are systematically compared and validated through experiments. Our results will shed light on the rational usage of amyloid inhibitors in clinic.