# Oklahoma ACE: Molecular Deconstruction of Autoimmune Disease to Aid Clinical Trial Success

> **NIH NIH UM1** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2020 · $87,400

## Abstract

Project Summary
 The Oklahoma ACE (OACE) strives to understand the biology of autoimmune diseases through
interdisciplinary, collaborative research that integrates clinical and basic questions. This prior ACE work has
led to 128 publications, including 42 with authors from 2 or more ACEs, leadership of a previous and ongoing
ACE clinical trial and lead or near lead recruitment in three ACE trials while a Basic ACE. We build on this
expertise through this UM1 Clinical ACE submission. Although significant progress in unveiling mechanisms of
autoimmune disease pathogenesis has been made, development of targeted therapies is critically lacking. For
autoimmune disease therapeutic development to succeed and patient outcomes to improve, deepened
understanding of molecular disease heterogeneity, therapeutic pharmacobiology and improved trial designs
are needed. The Oklahoma ACE will pursue a novel, comprehensive theme of accelerating discovery and
translation by deconstructing molecular heterogeneity to enrich for patients with common molecular pathways,
partnered with repurposed therapies from other fields and novel trial designs which eliminate confounding
background polypharmacy, to address these unmet needs.
 Our primary clinical project utilizes our innovative SLE trial design which uses serial depomedrol
injections to suppress disease, halting of background immunosuppressive drugs to provide a more pristine
environment to test the effectiveness of mycophenolate mofetil with or without add-on of tacrolimus to
suppress SLE activity. Partnered mechanistic studies will test our soluble mediator flare index and other select
activated immune cell subsets for the ability to predict upcoming flare, as well as to test specific hypotheses of
MMF response/resistance and of SLE disease flare mechanisms. Preliminary data in our alternate clinical
project has found critical roles of neutrophils in neuromyelitis optica, a complex autoimmune disease where up
to 40% of patients have continual relapse and damage even with treatment with B cell depleting therapies and
steroids. Pre-clinical work from this team has shown efficacy in two animal models of alpha-1 anti-trypsin,
which inhibits neutrophil elastase. This first-in-NMO study will assess effectiveness and safety, as well as
mechanistic studies which test biologic mechanisms of treatment, predictors of response and molecular
mechanisms of NMO flare. Our collaborative project deconstructs molecular heterogeneity and associated
pathogenic mechanisms of disease in subgroups of SLE patients. Building on preliminary data which identifies
seven molecular subsets by gene expression profiling, soluble mediators and autoantibodies, proposed studies
will test hypotheses of specific molecular mechanisms through deep immunophenotyping and single cell
technologies such as scRNAseq, CITE-seq, CyTOF and ChipCytometry. These projects, facilitated by our
Admin Core, will study fundamental aspects of autoimmunity and conduct foc...

## Key facts

- **NIH application ID:** 9901415
- **Project number:** 5UM1AI144292-02
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** JUDITH A JAMES
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $87,400
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9901415

## Citation

> US National Institutes of Health, RePORTER application 9901415, Oklahoma ACE: Molecular Deconstruction of Autoimmune Disease to Aid Clinical Trial Success (5UM1AI144292-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9901415. Licensed CC0.

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