Skip to main content

Pharmacokinetics and CNS Distribution of IgG Antibodies: Quantitative Comparison of Blood-brain, Blood-CSF and CSF-brain Relationships After Intranasal and Intravascular Dosing

Study Rationale:                             
Immunotherapy using antibodies (large proteins) directed against alpha-synuclein is a promising, potentially disease-modifying treatment approach for Parkinson’s disease (PD). However, achieving reliable, chronic central nervous system (the brain and spinal cord) delivery for molecules, such as antibodies, represents a major challenge. The goal of this study is to provide a comprehensive evaluation of the delivery and distribution of antibodies after intranasal (through the nose) and intravascular (through the veins) administration. We will compare the two routes across a range of administered doses and time points, providing one of the first-ever direct comparisons of each approach.

We hypothesize that intranasally-administered antibodies may provide a significant targeting advantage over other administration routes. Identification of a superior adminsitration route would allow for the potential to alter the course of Parkinson’s progression by achieving therapeutically-relevant antibody concentrations.

Study Design:
We will determine brain levels of antibodies following intranasal or intravascular application in pre-clinical models. We will also evaluate different doses of the antibodies with either a radioactive or fluorescent label (tags to track the delivery of the protein) and administer them with and without a novel, physiologic absorption enhancer that we recently identified. Brain, cerebrospinal fluid, blood and peripheral tissue levels will be measured and mapped using multiple techniques. In summary, we will comprehensively assess the targeting efficiency of the intranasal route compared to intravascular application across a range of doses and time points.

Impact on Diagnosis/Treatment of Parkinson’s Disease:                              
Delivering antibodies capable of binding to alpha-synuclein and clearing it from the brain could potentially neutralize, prevent or perhaps even reverse the Lewy pathology and neurodegeneration that are the hallmarks of the disease.

Next Steps for Development:
This project will allow us to obtain critical, quantitative central and systemic distribution data for intranasally-applied antibodies, establish the feasibility of such a strategy for developing PD immunotherapies and determine correct dosages for future studies using pre-clinical models of PD. This study will also provide critical data to support current systemic immunotherapy clinical trials.


  • Robert G Thorne, PhD

    Madison, WI United States

Discover More Grants

Within the Same Program

Within the Same Funding Year

We use cookies to ensure that you get the best experience. By continuing to use this website, you indicate that you have read our Terms of Service and Privacy Policy.