Methods and Compositions for Treatment and Patient Stratification of Fibrotic Disease by Non-Kinase Reversal of a Periostin-Anchored Activated Myofibroblast Cell State (Provisional Patent Specification)

Specification of U.S. Provisional Patent Application No. 64/128,961 (filed August 10, 2026; inventor Glen Charles Ritschel, Ritschel Research), archived as a citable, timestamped defensive-publication disclosure. This disclosure describes a single-cell RNA-sequencing-derived, periostin-anchored 18-gene signature of an activated, matrix-secretory myofibroblast cell state that is the shared pathogenic effector across a genus of fibrotic diseases of the skin, fascia, liver, and lung. Measured compositionally — as the fraction of fibroblasts occupying the cell state, so the read is robust to the constitutive matrix expression of resting fibroblasts — the cell state is markedly expanded relative to healthy tissue across keloid and hypertrophic scar, Dupuytren disease and related fibromatoses, the fibrotic component of hidradenitis suppurativa, and systemic sclerosis skin (on the order of 33–95% of fibroblasts versus ~0.8% in healthy skin), and its shared matrix-secretory program is elevated in the genuine myofibroblasts of skin, liver, and lung, while remaining near baseline in non-fibrotic inflammatory disease of the same tissue. The disclosure provides the signature; a compositional method of measuring the cell state; a method of selecting non-kinase agents that reverse it (aryl-hydrocarbon-receptor agonists such as tapinarof, PPAR-gamma agonists such as pioglitazone, and collagen-synthesis inhibitors such as halofuginone); methods of treating a member of the genus with such agents as tissue-localized compositions; and a periostin-anchored stratification biomarker defining a responder subgroup rather than an all-comers population. Discovery-stage computational work: the disease-associated expansion of the cell state is validated in independent public human single-cell data, while reversal of the state by the named agents is mechanism-anchored and not yet demonstrated preclinically or clinically. Not medical or legal advice.