Method2Model — Stage-2 Package: Dual-Platform mRNA Therapy in X-Linked ALD (Formula Pack, I/O Contract, Explainer)

This deposit contains the Stage-2 modeling package for a dual-platform mRNA therapy in X-linked adrenoleukodystrophy (ALD), developed within the Method2Model framework. It builds on earlier Stage-0 (Feasibility / Assumptions) and Stage-1 (Architecture) work and focuses on making the model implementation-ready by locking down the equations and the input/output interface before coding.

The package is centered on a dual-platform design (LNP + EV, peripheral-first → CNS) and describes how restoring functional ALDP (ABCD1) in relevant cell types propagates through VLCFA reduction, neuroinflammation, axonal injury, and translational endpoints such as NfL and Loes score. It is intended as a worked example of how complex translational protocols can be turned into explicit, reviewable modeling assets that support de-risking and design decisions.

Contents

This Stage-2 package includes three tightly linked documents:

• Stage-2 Formula Pack (PDF)
  Full mathematical formulation of the model architecture (Blocks A–G), including state definitions, ODEs, algebraic maps, boundary/initial conditions, and decision criteria (Go / No-Go / Pivot) under uncertainty.

• Stage-2 I/O Contract (PDF)
  The official schema for implementation: file names, formats (CSV / YAML / HDF5 / JSON), column names, types, units, ranges, and block-to-file mapping. This document is designed to be “Formula Lock”–ready so that coding can proceed without scope creep.

• Stage-2 Model Explainer (PDF)
  A non-technical narrative aimed at medical and translational researchers (PI, clinical scientist, pharmacology, CMC). It explains what each block does, what questions it answers, and how the inputs/outputs map back to protocol, CMC, and cohort design.

Intended use and limitations

This deposit is provided for research and educational use as an example of a Stage-2 modeling deliverable. It is not a clinical protocol, not a substitute for regulatory guidance, and not production software. Numerical values, where present, are illustrative and should not be interpreted as recommended doses or clinical thresholds.

For commercial use, redistribution, or inclusion in paid consulting or R&D deliverables, please follow the license terms associated with this record and/or contact Method2Model to obtain permission.

Zenodo DOI for this Stage-2 package: 10.5281/zenodo.18093206.