SBIR-STTR Award

Nanoparticles for Detecting Noradrenergic Neurons in Alzheimer's Disease
Award last edited on: 1/19/2021

Sponsored Program
STTR
Awarding Agency
NIH : NIA
Total Award Amount
$266,683
Award Phase
1
Solicitation Topic Code
-----

Principal Investigator
Puliyur Mohankumar

Company Information

S G Endocrine Research LLC

200 Fortson Drive
Athens, GA 30606

Research Institution

----------

Phase I

Contract Number: 1R41AG069539-01
Start Date: 8/15/2020    Completed: 7/31/2021
Phase I year
2020
Phase I Amount
$266,683
Alzheimer's disease (AD) is a progressive neurological disorder that is marked by the presence of amyloid-ß plaques, neurofibrillary tangles and cognitive deficits. The economic impact of this disease is staggering and is expected to exceed $1 trillion dollars by the year 2050. Early diagnosis and treatment can substantially reduce the economic burden related to AD. Specifically, being able to assess early pathological changes in specific brain areas could be beneficial for diagnosis and treatment. The locus coeruleus (LC), which provides the majority of the noradrenergic innervation to areas such as thalamus, cortex and hippocampus, undergoes extensive neurodegenerative changes. These changes that occur in the LC have been described as the earliest pathologies observed in AD and, critically, appear at least a decade ahead of the neurocognitive deficits. LC noradrenergic neurons are involved in regulating key neurobehavioral functions such as cognition, arousal and wakefulness. However, assessing changes in LC over the course of AD in patients remains a major challenge. The main objective of the proposed research in phase 1 is to develop an organic nanoparticle-based MRI imaging agent to non-invasively monitor noradrenergic neurons in the LC using a preclinical model of AD. Our preliminary studies provide evidence that these nanoparticles are taken by noradrenergic neurons in the brainstem and facilitate the imaging process. Our specific aims are to 1. To assess the ability of the nanoparticles to image the LC using MRI, and correlate with changes in norepinephrine levels. 2. To assess whether these particles can be used to measure degenerative changes as the disease progresses. Translating this to larger animal models and conducting preclinical testing will be next step following this STTR.  

Public Health Relevance Statement:
Proposal narrative: The proposal aims to develop imaging modalities that can monitor changes in brainstem using a novel nanoparticle-based imaging agent. This nanoparticle is small enough to cross the blood brain barrier and is actively taken up by catecholaminergic neurons. It has the capacity to transform how neurological and psychological disorders are diagnosed, monitored and treated. Specifically, this will help monitor the locus coeruleus, a noradrenergic area of the brain, which shows the earliest pathological changes in Alzheimer's disease.  

Project Terms:
Affect; Age; age related; Alzheimer's Disease; Alzheimer's disease model; American; Amino Acid Neurotransmitters; Amyloid beta-Protein; Anabolism; Animal Model; Area; Arousal; Basal Nucleus of Meynert; base; Behavioral; Biological; biomaterial compatibility; Biopsy; Blood - brain barrier anatomy; Brain; Brain imaging; Brain Stem; Cannulas; Caregivers; Catecholamines; Cerebral cortex; Characteristics; cholinergic; Cognition; Cognitive; Cognitive deficits; Contrast Media; cost effective; Cost of Illness; design; Diagnosis; Disease; Disease Progression; Early Diagnosis; Early treatment; Economic Burden; economic impact; Functional disorder; Goals; Healthcare Systems; High Pressure Liquid Chromatography; hindbrain; Hippocampus (Brain); Human; Human Amyloid Precursor Protein; Image; imaging agent; imaging capabilities; imaging modality; implantation; innovation; Levodopa; Ligands; locus ceruleus structure; Magnetic Resonance Imaging; Magnetism; Measures; Memory Loss; Mental disorders; Methods; Modality; Monitor; mutant; nanoparticle; Nanostructures; Near-infrared optical imaging; Nerve Degeneration; nerve supply; nervous system disorder; neurobehavioral; Neurocognitive; Neurocognitive Deficit; Neurodegenerative Disorders; Neurofibrillary Tangles; Neurons; Neurotransmitters; non-invasive imaging; non-invasive monitor; noradrenergic; Norepinephrine; novel; Operative Surgical Procedures; Optics; Outcome; particle; Pathologic; Pathology; Patients; Phase; Phenylalanine; Positron-Emission Tomography; Pre-Clinical Model; Preclinical Testing; presenilin-1; Process; Property; Prosencephalon; Quality of life; Rattus; Research; Resolution; Sampling; Small Business Technology Transfer Research; Structure; tau Proteins; temporal measurement; Testing; Thalamic structure; Therapeutic Intervention; Three-Dimensional Imaging; Tissues; tool; Translating; Wakefulness

Phase II

Contract Number: ----------
Start Date: 00/00/00    Completed: 00/00/00
Phase II year
----
Phase II Amount
----