Use of fluorescent ANTS to examine the BBB-permeability of polysaccharide

Description:

Project ID:  D2015-27

Invention Description: Methods of generating and administering digestion products of FDA-approved low acyl gellan gum (LA-GAGR) to produce neuroprotective mega-GAGR, midi-GAGR, and mini-GAGR and administration thereof.

Applications: Compositions comprising midi and/or mini-GAGR have been shown to be useful for treatment of neurodegenerative disorders including Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, spinal cord injury, and brain trauma. In addition, methods are also available to examine the BBB-permeability of polysaccharides including products of LA-GAGR.

 

Novelty: Midi-GAGR has several desired properties (neurotrophic, anti-oxidant, non-cytotoxic, anti-inflammatory, and BBB-permeable) for treatment of neurodegenerative diseases. Such materials have been shown to cross the blood-brain barrier, reduce the degeneration of cortical, peripheral, and dopaminergic nerve cells under pathogenic conditions, and, likely, alleviate the symptoms of neurodegenerative diseases in advanced stages, as well as reverse, prevent or at least significantly delay the extinction of cortical, peripheral and dopaminergic nerve cells in the early stages of such disorders.

 

Value proposition:

·       Materials described include polysaccharide digestive products resulting from the enzymatic hydrolysis of low acyl gellan gum (LA-GAGR). 

o   LA-GAGR is already approved by the FDA and used as a food additive, cosmetics and pharmaceuticals with few side effects in humans, even at high doses (~200 mg/kg);

o   LA-GAGR exhibits good oral bioavailability, is relatively stable in serum, as well as biodegradable and cost effective.

·       The mechanism by which midi-GAGR exerts its neuro-regenerative action is clear; midi-GAGR uses two neurotrophic receptors for its neuroprotective and neurotrophic actions.

·       ANTS (8-aminonaphthalene-1,3,6-trisulfonic acid disodium salt)-tagged midi-GAGR enters the brain and blood circulation, maintains its intact structure inside the animal and does not bind to serum protein for at least six hours after intranasal administration.

·       Treatment with midi-GAGR protected rodent cortical neurons and neuro2A cells from cell death caused by amyloid beta peptide, hydrogen peroxide, and lipid peroxide. Moreover, treatment with midi-GAGR increased neuritogenesis and nuclear accumulation of phosphorylated CREB, a transcriptional factor that activates gene expression for neuronal survival and neurogenesis, in cortical neurons.

·       Animal data for the BBB-permeability and neurotrophic effect in vivo of midi-GAGR is available.

Patent Information:
Category(s):
For Information, Contact:
Stephen Snider
AVP Tech Transfer
The University of Toledo
419 530 6225
Stephen.Snider@utoledo.edu
Inventors:
Joshua Park
Kevin Christopher
Vishruti Makani
Keywords:
ALS
Alzheimer’s disease
Blood-brain Barrier
Brain Trauma
Neuritogenesis
Neurodegenerative
Neuroprotective
Spinal Cord Injury