Targeted nanotherapies for the treatment of brain disorders
Active Project Grant Awarded Last action
- Award ID
- R01NS140172
- Recipient
-
Washington State University UEI XRJSGX384TD6
- Awarding agency
-
National Institute of Neurological Disorders and Stroke
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,064,423
Award facts
- Assistance listing
- 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
- Completion date 26% complete
- Place of performance
- Pullman, WA 99164, USA
Award details come from USAspending.gov.
Description
- Abstract
- The delivery of small molecule therapeutics across the blood brain barrier (BBB) is difficult, making the development of therapies for neurological diseases very challenging. Even if the drugs or nanoparticles cross the impaired BBB following brain injury, targeting key cells involved in the brain diseases, such as, neurons present significant challenges. Targeting neurons is specifically complex since they are far lower in number and less phagocytic in nature compared to the glial cells. Moreover, neurons exist in a variety of types that perform specific functions in the brain which makes targeting specifically the injured neurons more difficult. We have designed and developed a novel tailor-made 2-deoxy-d-glucose (2DG) based glycodendrimer nanoplatform (2DG-d) that addresses these challenges by targeting and delivering drugs to neurons selectively at the site of brain injury. Our preliminary data suggest that the fluorescently labeled 2DG-d demonstrates neuronal targeting and specifically localizes within the neurons across the BBB at the site of injury in the brain from systemic administration in a mouse model of pediatric traumatic brain injury (TBI). The 2DG-d technology is designed to selectively deliver high payloads of drugs to affected neurons and microglia across the BBB, and to simultaneously achieve in vivo stability, high water solubility, ease of scalability, and flexibility in single or multiple drugs delivery. Our unique platform builds on our expertise in designing clinically relevant nanomaterials for drug delivery applications. We further show that a single systemic dose of a conjugate of 2DG-d and pioglitazone (PIO) a ppar- γ agonist (2DGD-PIO) improves behavioral outcomes and neuroinflammatory responses in a pediatric mouse model of TBI. PIO is an anti-diabetic drug being widely investigated for brain diseases, including TBI. However, its poor aqueous solubility and peripheral side-effects are a concern that can be addressed using 2DGDN mediated targeted delivery. The goal of this R01 proposal is to develop a neuron-targeting 2DGD-PIO conjugate and validate the efficacy in pediatric TBI model to treat, preserve, and restore neuronal function, with significant implications for other brain disorders. Our ultimate long-term objective is to develop scalable, systemic 2DGD-drug therapies with improved efficacy and reduced systemic side effects that can be used not only for TBI but other brain diseases as well. We will achieve our goal through the following three aims: aim 1: demonstrate reproducible synthesis and evaluate mechanism of uptake of 2DG and 2DGD-PIO conjugates; aim 2: assess in vivo biodistribution, pharmacokinetics and toxicity of 2DG and 2DGD-PIO; and aim 3: short and long-term efficacy of 2DGD-PIO conjugate in a TBI mouse model.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $532,038 | |
| Original award | $532,385 |
Quick answers
Who received award R01NS140172?
R01NS140172 was awarded to Washington State University by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on August 1, 2025.
How much is award R01NS140172 worth?
$1,064,423 has been obligated on R01NS140172.
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