Treatment of CNS damage from non-disordered drug use with drhq, a novel regulator of CD74 signaling

The National Institute on Drug Abuse awarded Virogenomics Biodevelopment, Inc. $399,889 on June 1, 2026, under the Drug Use and Addiction Research Programs (CFDA 93.279) to evaluate DRHQ, a novel CD74-targeting immunotherapeutic compound, for treatment of methamphetamine-induced central nervous system damage.

The award funds preclinical research and development activities across two aims. In Aim 1, the recipient will evaluate whether DRHQ reduces infarct volume and improves cognitive function in animal models of methamphetamine-associated stroke. In Aim 2, the recipient will examine the impact of methamphetamine exposure on myelinated and unmyelinated axon function in the corpus callosum and determine whether DRHQ can reverse any resulting axonal dysfunction and loss of integrity.

DRHQ is a third-generation molecule optimized for CD74 binding and future clinical use. Prior animal model work has demonstrated that CD74-targeting constructs improve cognitive function and decrease inflammation associated with methamphetamine exposure, reverse axonal dysfunction in multiple sclerosis models, and reduce infarct volume following stroke.

The period of performance runs from June 1, 2026, through May 31, 2027. Work is performed in Oregon. The assistance type is a Project Grant, classified under the SBIR/STTR program framework. Virogenomics Biodevelopment, Inc. is a woman-owned small business based in Tigard, Oregon, specializing in preclinical and clinical-stage CD74-targeted immunotherapeutic drug development for central nervous system and stimulant use disorders.

Abstract

Non-disordered drug use (nddu) is a severe public health concern. Stimulants like methamphetamine cause long-term damage to regions of the brain that regulate cognitive functions, psychiatric symptoms, and promote drug-seeking behavior. Methamphetamine use increases the risk of stroke and damage to white matter (WM), both of which can impact cognitive function. 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 of methamphetamine use. These constructs have a therapeutic impact in animal models of stroke and can reverse the axonal dysfunction observed in a mouse model of multiple sclerosis. These constructs also have been shown to improve cognitive function and decrease the inflammation associated with exposure to methamphetamine, suggesting a highly effective therapeutic profile. Methamphetamine has been shown to exacerbate the increased infarct volume and decreased cognitive function observed following transient middle cerebral artery occlusion in mice. The direct effects of methamphetamine use on white matter function and vulnerability to ischemia remain unexplored. The primary objective of this sttr proposal is to evaluate our third-generation molecule, drhq, which has been optimized for CD74 binding and future clinical use, by determining whether IT can reduce or even reverse neuronal and axonal damage caused by methamphetamine use. In aim 1, we will evaluate whether drhq decreases infarct volume and improves cognitive function from methamphetamine-associated stroke. In aim 2, we will examine the impact of methamphetamine alone on the function of myelinated and unmyelinated axons in the corpus callosum from mice, and then, we will determine whether any reduction in axon function and integrity can be reversed following treatment with drhq. At the end of this phase 1 feasibility study, we will have determined whether drhq has the potential to be an effective treatment for neuronal and axonal damage caused by methamphetamine use including whether IT can reduce or reverse the severity observed in methamphetamine-associated stroke. If successful, drhq may be a valuable therapeutic in treating complications from methamphetamine use. Phase 2 studies would look to expand preclinical testing and work to advance drhq into clinical testing.