Apr 2, 2020

A quantitative model for oral administration of living therapeutics

BioRxiv : the Preprint Server for Biology
Z. J. Mays, Nikhil Unni Nair

Abstract

As medicine shifts toward precision-based and personalized therapeutics, utilizing more complex biomolecules to treat increasingly difficult and rare conditions, microorganisms provide an avenue for realizing the production and processing necessary for novel drug pipelines. More so, probiotic microbes can be co-opted to deliver therapeutics by oral administration as living drugs, able to survive and safely transit the digestive tract. As living therapeutics are in their nascency, traditional pharmacokinetic-pharmacodynamic (PK-PD) models for evaluating drug candidates are not appropriate for this novel platform. Using a living therapeutic in late-stage clinical development for phenylketonuria (PKU) as a case study, we adapt traditional oral drug delivery models to properly evaluate and inform the engineering of living therapeutics. We develop the adapted for living therapeutics compartmental absorption and transit (ALT-CAT) model to provide metrics for drug efficacy across nine age groups of PKU patients and evaluate model parameters that are influenced by patient physiology, microbe selection and therapeutic production, and dosing formulations.

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Mentioned in this Paper

Microarray Analysis
Pluripotent Stem Cells
Genes
Gene Expression
Cell Differentiation Process
Study of Epigenetics
Cellular Reprogramming
Induced Pluripotent Stem Cells
Insight
Cell Type

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