# Novel Glucose dendrimers for targeting injured neurons

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $519,500

## Abstract

Project Summary
Preserving and repairing injured neurons is the primary goal of treatments for brain injuries. Yet, delivering
therapeutics specifically to neurons has been a challenge due many factor. Increased glucose uptake and its
hypermetabolism, is a hallmark of injury or evolving injury in neurons in many pathological conditions (e.g.
seizures, stroke, trauma). Delivering drugs specifically to injured neurons in the area of pathology, would
address a significant gap in neuroprotective approaches, opening new treatment avenues for acute CNS
disorders. We seek to address this gap by developing novel dendrimers that take advantage of altered glucose
transport in injured neurons, without a need for a targeting ligand or antibody.
Previously, our group developed hydroxyl polyamidoamine (PAMAM) dendrimers that specifically targeted
reactive brain microglia/macrophages and attenuated neuroinflammation and injury in multiple models of brain
injury, and now are in early Phase 2 clinical trials. This application aims to develop and validate a novel
dendrimer made primarily from glucose that preferentially targets injured neurons. We have designed non-
degradable dendrimers made primarily of glucose building blocks, that can facilitate enhanced uptake due to
multivalent surface interactions with glucose transporters. We hypothesize that glucose dendrimers will localize
primarily into injured neurons, enabling sustained delivery of drugs for neuroprotection and preventing neuronal
loss. Importantly, our preliminary data, with a generation-2 glucose dendrimer (GD2) with 24 glucose
molecules on the surface, suggests that they specifically localize in injured/active neurons in vitro and four
clinically-relevant, diverse in vivo models of acute neuronal injury. Glucose dendrimer-ketamine conjugate
(GD2-ket) is more effective than ketamine alone in suppressing clinical seizures in an established rodent
epilepsy model. We will test our hypothesis by performing experiments in the following aims: Aim 1: Determine
the extent and specific mechanisms of glucose-dendrimers (GD) uptake in neurons. Aim 2: Evaluate in vivo
cellular biodistribution and pharmacokinetics (PK) of systemic glucose-dendrimers in a mouse model of acute
neuronal injury induced by epilepsy; Aim 3: Determine efficacy of glucose-dendrimer-ketamine conjugates in
rodent model of epilepsy. The proposed glucose dendrimer platform can impact treatments for multiple CNS
disorders, especially in the acute phase, opening new avenues for nanomaterials. Our team has the
combination of dendrimer nanomedicine, neuroscience, epilepsy, and brain injury expertise to carry out the
proposed studies and enable translation from the bench to bedside.

## Key facts

- **NIH application ID:** 10972937
- **Project number:** 1R01NS139204-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Sujatha Kannan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $519,500
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10972937

## Citation

> US National Institutes of Health, RePORTER application 10972937, Novel Glucose dendrimers for targeting injured neurons (1R01NS139204-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10972937. Licensed CC0.

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