# Modeling drugs of abuse-HIV-AD interactions using iPSC-derived neural cells

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2024 · $453,841

## Abstract

Summary
 This is an “Administrative Supplement Program to Help Develop Alzheimer’s-Focused NIH Grants” in
response to NOT-AG-23-032.
 Emerging neuropathology findings in neuroHIV as well as gene expression results from our group suggest
a degree of pathogenic similarity and possibly overlap between neuroHIV and Alzheimer’s Disease (AD).
Additionally, the abuse of opioids like heroin, oxycodone and fentanyl and stimulants like cocaine and
methamphetamine (METH) is believed to increase the risk of dementias including AD. However, experimental
evidence of the detrimental interaction of drugs of abuse and AD are quite limited, particularly in the setting of
HIV. To address these knowledge gaps, paralleling and integrating the parent grant, we propose to use in vitro
AD models consisting of induced pluripotent stem cells (iPSCs)-derived neural tri-cultures treated with amyloid
β 1-42 oligomers and iPCS-derived tri-cultures harboring isogenic APOE alleles, which are key genetic
determinants of AD risk and to expose them to either an opioid (morphine) or a stimulant (METH) in the same
general design of the parent grant. This Supplement will add AD-focused studies to the experimental design of
the parent grant, that does not propose AD/ADRD-focused experiments.
 This research grant qualifies for the present Supplement under NOT-AG-23-032 because the parent grant
is on a related topic (per NOT-AG-23-032): pathogenesis of cognitive decline in neuroHIV and drug abuse
comorbidity that are believed to share pathogenic mechanisms and be additive to cognitive decline in AD. The
proposed aims closely parallel the parent grant’s with the addition of iPCS models of AD. The parent grant
uses iPSCs-derived neural tri-cultures to model HIV-drug abuse interactions but does not propose AD/ADRD-
related studies. This Supplement will generate preliminary results for an upcoming R01 application focused on
the detrimental interactions of AD with HIV and substance abuse.

## Key facts

- **NIH application ID:** 10940557
- **Project number:** 3R01DA053801-04S1
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Vez REPUNTE-CANONIGO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $453,841
- **Award type:** 3
- **Project period:** 2021-09-30 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10940557

## Citation

> US National Institutes of Health, RePORTER application 10940557, Modeling drugs of abuse-HIV-AD interactions using iPSC-derived neural cells (3R01DA053801-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10940557. Licensed CC0.

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