University of South Florida

The United States Government As Represented by the Department of Veterans Affairs

Umesh Kumar Jinwal

Bill J Baker

Laurent Calcul

Chad Dickey

Vijaykumar Bhadabhai Sutariya

Matthew Lebar

Vetriselvan Manavalan

Malathi Narayan

Diego A Peralta

Nanoparticle based MKT formulation. MKT is encapsulated by poly(ethylene glycol)ylated (PEGylated) poly-(lactide-co-glycolide) (PLGA) to form nanoparticles (NPs). To induce trans-BBB permeability, glutathione (GSH) is coated on the resulting NPs. Newly generated MKT-NPs showed BBB permeability and tau reduction in experimental models. Specifically, brain-targeting MKT NPs were developed with a glutathione coating, characterized, and shown to permeate BBB permeation insert models as a therapeutic for Alzheimer's disease and related tauopathies.

Glutathione-coated nanoparticles for delivery of MKT-077 across the blood-brain barrier

A delivery system of coated and uncoated nanoparticles (NP) for delivery of methylene blue (MB). The delivery system was developed using PLGA-based polymer that was repeatedly shown to be biocompatible and biodegradable. The parameters of synthesized NPs were within the suitable range for BBB permeation&#x2014;specifically, the NPs were monodispersed, with slight negative charge, and with the size within 100-150 nm range suitable for intravenous delivery and delivery to the brain. The coating on the nanoparticle did not have a significant impact on the nanoparticle size and zeta potential. Based on the immunoblotting experiments using AD cellular model, the GSH coated NPs were better in reducing tau levels compared to MB solution. In vitro BBB Transwell permeation study showed eight fold higher MB-NP permeation compared to the MB solution over 24 hours.

Preparation and characterization of methylene blue nanoparticles for Alzheimer's disease and other tauopathies

Disclosed herein are compositions and methods for treating tauopathies such as Alzheimer's disease (AD). Also provided herein are methods of reducing or disrupting tau aggregation in a subject, and methods of reducing tau protein in a subject. The methods may include administering to the subject a therapeutic amount of hexachlorophene, or a pharmaceutically acceptable salt thereof. Further provided herein are pharmaceutical compositions comprising hexachlorophene, or a pharmaceutically acceptable salt thereof, for the treatment of a tauopathy in a subject.

Compositions and methods for the treatment of tauopathies

The subject invention pertains to myricanol derivatives, therapeutic compositions, and methods for treatment of neurodegenerative diseases, in particular, neurodegenerative diseases associated with abnormal accumulation of protein tau.

Myricanol derivatives and uses thereof for treatment of neurodegenerative diseases

A method of treating TDP-43 proteinopathies such as Alzheimer's disease, amyotrophic lateral sclerosis, and fronto-temporal lobar dementia is presented herein. It was found that administering hexachlorophene to cells expressing endogenous TDP-43 or overexpressing wild-type TDP-43 reduced accumulation of TDP-43 in the cells.

Method of treating TDP-43 proteinopathies using hexachlorophene

A method of treating a disease associated with mutation of LRRK2 protein is presented herein. It was found that administering hexachlorophene to cells expressing endogenous LRRK2 or overexpressing wild-type or mutant LRRK2 reduced the total LRRK2 level in the cells.

Method of treating diseases associated with LRRK2 mutation using hexachlorophene

Aspects of the invention pertain to chemical compounds, therapeutic compositions, and methods for treating neurodegenerative diseases, in particular, neurodegenerative diseases associated with abnormal accumulation of protein tau.

Growing community of inventors

Tampa, FL, United States of America

Umesh Kumar Jinwal