# Precision medicine approaches to chronic inflammatory skin disease of older veterans

> **NIH VA I01** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2024 · —

## Abstract

Inflammatory dermatologic disease increases in the elderly due to aging-related dysfunctional
cutaneous alterations. Given the aging population of the U.S. and veteran population, it is
imperative to improve understanding and optimize treatment choice for elderly skin diseases. In
this proposal, we focus on atopic dermatitis (AD) of the elderly, an understudied inflammatory
skin disease subgroup with significant disease burden and an estimated prevalence of ~5-11%
amongst individuals over 65 years of age. While the distinct molecular features of elderly AD are
still undercharacterized, it appears to include lesser Th2 and increased Th17 inflammatory
activation relative to classic childhood-onset AD. Increasingly, inflammatory skin disease is
being treated with therapies targeting specific inflammatory pathways (e.g. Th2-directed IL-4Rα
blockade in atopic dermatitis); however, low precision in defining patient-level disease
mechanism contributes to treatment failure. ~30% of patients do not completely respond to a
given targeted immunomodulatory drug, likely because of the pervasive genetic heterogeneity
underlying these diseases of immunological overactivity. The fundamental unmet need in
inflammatory disease is the ability to precisely determine molecular pathology of individual
patients. Identification of patient-level biomarkers in chronic inflammatory disease has been
hindered by A) a greater role of epigenetics (i.e. RNA levels) compared to easily assayed DNA
variants and B) poor molecular resolution resulting from profiling of mixed immune and stromal
cells. The goals of this proposal are to 1) define molecular abnormalities underlying atopic
dermatitis of the elderly and how they change with IL-4Rα blockade treatment and 2) develop a
precision medicine approach for choosing optimal targeted treatment for individual cases of
elderly atopic dermatitis, a molecular framework that can eventually be extended to any chronic
inflammatory disease. Our genomics-experienced team is qualified to accomplish these goals
based on our discovery of single cell RNA-sequencing derived transcriptional signatures in
atopic dermatitis and psoriasis vulgaris, as well as successful genetic dissection of other
complex skin diseases.

## Key facts

- **NIH application ID:** 10929936
- **Project number:** 5I01CX002608-02
- **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO
- **Principal Investigator:** Jeffrey B Cheng
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10929936

## Citation

> US National Institutes of Health, RePORTER application 10929936, Precision medicine approaches to chronic inflammatory skin disease of older veterans (5I01CX002608-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10929936. Licensed CC0.

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