# CSF Oligomeric α-synuclein targeted nano scavengers as a Parkinson's disease theranostic

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $799,127

## Abstract

Project Summary
The pathogenesis of Parkinson’s disease (PD) and related synucleinopathies such as dementia with Lewy bodies are
characterized by progressive deposition Lewy bodies and Lewy neurites composed primarily of phosphorylated alpha-
synuclein aggregates (α-syn), neuroinflammation, blood-brain barrier compromise, and neurodegeneration. Currently, there
are no clinically approved biomarker diagnostic tools or disease modifying treatments for PD. Clinical diagnosis is based
on a combination of motor and nonmotor symptoms, but the neurodegeneration process may precede the first appearance
of these symptoms by decades. Empirical data suggests that levels of oligomeric α-syn in the cerebrospinal fluid (CSF) of
PD patients surpass those of normal individuals by several orders of magnitude. Oligomeric α-syn and reactive gliosis are
strongly implicated in the initiation and spread of the disease. Recent data from clinical trials with anti-amyloid-β (anti-Aβ)
monoclonal antibodies (mAbs) in Alzheimer’s disease (AD), (despite lack of clarity in the full safety/efficacy profile),
suggest that anti-Aβ mAbs statistically improved cognitive and biomarker outcomes, demonstrating that neurodegenerative
amyloidosis disorders can be slowed or halted. Over the past decade, we have demonstrated in several mouse models of
neurodegeneration that following tail vein injection, liposomes bearing an imaging contrast payload cross the BBB into the
CSF, primarily at the blood-CSF barrier at the at the choroid plexus and cerebrovascular leaks and bind to specific targets
within the brain, enabling separation of disease mice from controls using noninvasive magnetic resonance imaging (MRI)
or computed tomography imaging. Our lead product is currently in clinical trials as the first MRI-based imaging agents for
Aβ plaques in AD. In a recent proposal funded by the NIA (R21 AG067131), we hypothesized that a variant of our agent
labeled with oligomeric α-syn ligands will act as a scavenger for the pathologic species resulting in the formation of cross-
linked agglomerates of the agent and pathologic species making them more suitable substrates for rapid phagocytosis (sizes
> 0.5 microns) by activated glia. This in turn can lead to momentary accumulation of detectable levels of the agent in PD
positive brains enabling noninvasive separation of test subjects from controls. Our preliminary data demonstrates successful
in vitro formation of agglomerates upon exposure of the agent to α-syn fibrils and accelerated uptake of the ensuing
agglomerates by microglia and neuroblastoma cell lines. In vivo administration by tail vein injection followed by MRI
showed statistically significant signal enhancement in the brains of transgenic mice versus controls. The in vivo data was
verified by ex-vivo immunohistochemical analysis which showed a correlation between in vivo MRI signal, regional
distribution of the agent in brain tissue, Lewy pathology, and microglia activity. In this appl...

## Key facts

- **NIH application ID:** 11073370
- **Project number:** 1R01NS137633-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Eric Tanifum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $799,127
- **Award type:** 1
- **Project period:** 2024-09-18 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11073370

## Citation

> US National Institutes of Health, RePORTER application 11073370, CSF Oligomeric α-synuclein targeted nano scavengers as a Parkinson's disease theranostic (1R01NS137633-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11073370. Licensed CC0.

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