Method for improving delivery of immunotherapeutic agents to the CNS

­Background

Up to 1 billion people, suffer from neurological disorders, from Alzheimer (AD) and Parkinson disease, strokes, multiple sclerosis and epilepsy to migraine, brain injuries and neuroinfections. Most therapies fail mainly due to the poor penetration of the blood-brain barrier (BBB). Therefore, improving the delivery of drugs to the CNS is crucial to achieve success in managing these diseases. The glymphatic system acts as a macroscopic waste clearance system and utilizes a unique system of perivascular channels, to promote efficient elimination of soluble proteins and metabolites from the CNS. Besides waste elimination, the glymphatic system may also function to help distribute non-waste compounds, such as glucose, lipids and amino acids, among others. Manipulation of the glymphatic activity may represent a novel strategy for improving penetration of therapeutic agents, specially antibodies, to the CNS.

Technology Overview

We confirmed that the glymphatic system delivers tracers and antibodies brain-wide. The novelty of the study is that cerebrospinal fluid (CSF) tracer entry was enhanced ~3-fold by increasing the concentration of particles dissolved in the plasma (osmolality) without disruption of the BBB. Further, our study shows, in a mouse model for Alzheimer’s disease (AD), that changes in plasma osmolality enhanced the delivery of an amyloid-b (Ab) antibody, obtaining a 5-fold increase in antibody binding to Ab plaques. The Ab plaques are an indicator for disease progression in AD, so an increase in antibody binding could represent a promising result towards AD management and treatment.

Benefits

Noninvasive system that effectively enhances delivery of therapeutics in the CNS. This system uses substantially less antibody than required in previous studies, while achieving greater target engagement with possible fewer side effects.

Applications

Alzheimer and Parkinson disease, strokes, multiple sclerosis, epilepsy, migraine, brain injuries and neuroinfections.

URV Reference Number: 6-19014
Patent Information:
Category(s):
Therapeutic
For Information, Contact:
Cynthia Zhang
IP Attorney
University of Rochester
585-276-6600
cynthia_zhang@urmc.rochester.edu
Inventors:
Maiken Nedergaard
Benjamin Plog
Humberto Mestre
Tuomas Olavi Lilius
Andreas Tue Ingemann Jensen
Steven Goldman
Keywords: