# Immunotherapeutic Targeting CD74 as a Treatment for Stimulant Use Disorder

> **NIH NIH R41** · VIROGENOMICS BIODEVELOPMENT, INC. · 2024 · $405,334

## Abstract

Project Abstract
Methamphetamine is a highly addictive central nervous system (CNS) psychostimulant that causes long-term
damage to regions of the brain that regulate cognitive and psychiatric functions and promote drug-seeking
behavior and consequently, makes recovery from methamphetamine extremely difficult. The current standard of
care for stimulant use disorder (amphetamine-type, methamphetamine) is behavioral therapies but,
unfortunately, the majority of patients relapse to methamphetamine use within one year after treatment. There
are currently no FDA-approved therapeutics for methamphetamine addiction. Emerging evidence demonstrates
how immune factors can influence addictive behaviors and contribute to substance use disorders. We have a
collection of MHC class II constructs that bind to and downregulate the expression of CD74—the primary receptor
for macrophage migration inhibitory factor (MIF), a key inflammatory indicator in stimulant use disorder, as well
as other diseases. These constructs have therapeutic impact on drug-seeking behavior, and can also impact
cognitive function, and inflammation-associated with exposure to methamphetamine, suggesting a therapeutic
profile better than previously developed targets. The primary objective of this proposal is to evaluate our current
generation molecule, DRhQ, in preclinical animal models of stimulant use disorder. Within the drug development
process, DRhQ is moving from the lead optimization stage into the preclinical development stage. DRhQ, in its
final monomeric formulation, will be evaluated in this proposal demonstrating the feasibility of the molecule to be
used in clinical testing. Two animal models will be utilized to confirm cross-species efficacy. In rats, the impact
of DRhQ on cue-induced reinstatement following an extended access model will be evaluated. In mice, we will
use an established colony of Cd74 knockout and C57BL/6J control mice to evaluate the effects of DRhQ on
methamphetamine intake and preference (2-bottle choice test). We hypothesize that the effects of DRhQ
treatment in C57BL/6 mice will be similar to the effect of the Cd74 knockout on methamphetamine use,
confirming the mechanism of action for DRhQ. Key brain regions and plasma will be evaluated to identify
changes in protein expression following methamphetamine exposure and DRhQ immunotherapy. Collectively,
this research will help identify a biomarker for assessing DRhQ treatment response in patients with stimulant use
disorder or recovering from methamphetamine use. We expect that following the completion of this one-year
project, we will have definitive evidence that provides a strong rationale to advance the drug into clinical testing
as a treatment for stimulant use disorder.

## Key facts

- **NIH application ID:** 10932039
- **Project number:** 1R41DA059296-01A1
- **Recipient organization:** VIROGENOMICS BIODEVELOPMENT, INC.
- **Principal Investigator:** JENNIFER M LOFTIS
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $405,334
- **Award type:** 1
- **Project period:** 2024-06-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932039

## Citation

> US National Institutes of Health, RePORTER application 10932039, Immunotherapeutic Targeting CD74 as a Treatment for Stimulant Use Disorder (1R41DA059296-01A1). Retrieved via AI Analytics 2026-08-22 from https://api.ai-analytics.org/grant/nih/10932039. Licensed CC0.

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