# Dissociation of efficacy from side effects of anti-inflammatory therapies in Duchenne muscular dystrophy

> **NIH NIH P50** · CHILDREN'S RESEARCH INSTITUTE · 2020 · $266,529

## Abstract

Abstract:
Daily administration of high doses of glucocorticoids is standard of care for the treatment of many
pediatric inflammatory diseases, including Duchenne muscular dystrophy (DMD). The side effect profiles
of are severe, with stunting of growth, bone fragility, mood changes, and sleep disturbances, leading to a
decrease in quality of life of children, and an increase in the costs of clinical care. In preliminary data from
longitudinal studies of DMD patients, we describe validated panels of pharmacodynamic biomarkers for
multiple aspects of safety, as well as anti-inflammatory efficacy of glucocorticoids. Our group, in
collaboration with Reveragen biopharma, has also identified a dissociated glucocorticoid (VBP15) with
powerful anti-inflammatory and membrane stabilizing activity that is highly effective in ameliorating
disease phenotype in multiple inflammatory disease models including the dystrophin deficient mdx mouse.
Phase 1 clinical trials of VBP15 in 88 adult volunteers have shown safety up to a 30-fold prednisone dose
(20 mg/kg/day), with a relative loss of adrenal suppression, insulin resistance, and immune suppression.
The overarching goal of this project is to bridge safety and efficacy biomarkers to clinical outcomes so
that specific pharmacodynamic biomarkers can be used to facilitate the design and conduct of clinical
trials in younger DMD patients, 1-4 years old, where clinical outcomes are poorly established. To achieve
this goal we propose four specific aims 1). Bridge the novel putative safety and efficacy pharmacodynamic
markers to clinical outcomes using the existing CINRG DNHS natural history data, and sample set from
GC treated (pre and post) DMD patients; 2) define the differences in acute pharmacodynamics of GC vs.
VBP15 using single dose PK/PD time series in both adult volunteers and DMD patients, 3) validate and
qualify safety and efficacy biomarkers identified for GC and VBP15 treatment and 4) establish a Phase 2b
clinical trial protocol for 1-4 yr old DMD children, with inclusion of both established and novel safety and
efficacy biomarkers bridged to clinical outcomes in older children. This will set the stage for clinical trials
of VBP15 and other anti-inflammatory drugs, where the data obtained is expected to enable more acute
and objective readouts of drug action in pediatric patients using well-characterized and noninvasive
pharmacodynamic biomarkers as outcome measures.

## Key facts

- **NIH application ID:** 9970247
- **Project number:** 5P50HD090254-05
- **Recipient organization:** CHILDREN'S RESEARCH INSTITUTE
- **Principal Investigator:** YETRIB HATHOUT
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $266,529
- **Award type:** 5
- **Project period:** — → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970247

## Citation

> US National Institutes of Health, RePORTER application 9970247, Dissociation of efficacy from side effects of anti-inflammatory therapies in Duchenne muscular dystrophy (5P50HD090254-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9970247. Licensed CC0.

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