University of South Florida

The Charles Stark Draper Laboratory, Inc.

Javier Cuevas

Shivshankar Sundaram

Anilkumar Harapanahalli Achyuta

Chris Katnik

Vijaykumar Bhadabhai Sutariya

Alison Elizabeth Willing

Jon Clarence Antilla

Keith R Pennypacker

Emily Severance

Christopher Katnik

Michelle Cortes-Salva

A novel nanoparticle drug composition and method of use thereof is presented herein. The nanoparticle drug composition is comprised of at least one nanoparticle carrier, formed from the conjugation of PLGA and PEG, which encapsulates a drug such as afobazole and its derivatives, in a pharmaceutically acceptable carrier. The nanoparticle drug composition may be used to treat various diseases of the central nervous system involving excessive neuronal activity and inflammation such as stroke, Alzheimer's disease and anxiety.

Afobazole nanoparticles formulation for enhanced therapeutics

A method of treating stroke by administration of a novel sigma agonist is presented. Twenty-four hours after MCAO, systemic administration of several novel sigma agonists including: Bromo-DTG; Chloro-DTG; N,N'-di-1-Naphthylguanidine hydrochloride (NAGH); N,N&#x2032;-di-p-Nitrophenylguanidine HCL (NAD) or vehicle were injected subcutaneously daily for 3 days. Rats treated with Bromo-DTG and Chloro-DTG had no significant improvements in any of the motor or cognitive tests while NAGH treated rats showed improved vertical movement and had significantly less motor asymmetry and bias than vehicle treated rats. Sigma receptor agonist NAGH also was found to exert its long-term neuroprotective effects by preserving both gray matter and white matter tracts. Both NAD and NAGH, when administered 24 hours after experimental stroke, reduced neural damage and enhanced behavioral recovery thirty days later which suggests that NAGH and NAD potentially extend the therapeutic window of stroke several fold over the current treatments.

N,N'-di-1 naphthylguanidine HCl (NAGH) and N,N&#x2032;-di-p-nitrophenylguanidine HCl (NAD) treatment for stroke at delayed timepoints

This application provides devices for modeling ischemic stroke conditions. The devices can be used to culture neurons and to subject a first population of the neurons to low-oxygen conditions and a second population of neurons to normoxic conditions. The neurons are cultured on a porous barrier, and on the other side of the barrier run one or more fluid-filled channels. By flowing fluid with different oxygen levels through the channels, one can deliver desired oxygen concentrations to the cells nearest those channels.

Microfluidic device for generating neural cells to simulate post-stroke conditions

Disclosed is a novel composition and method for chemotherapy in leukemia. Activation of the calcium ion channel by tipifarnib increases intracellular calcium and triggers cell death in leukemia cell lines. Increasing the activity of this channel with 2-aminoethoxydiphenyl borate (2-APB) enhances both the intracellular calcium elevations and cell death, whereas decreasing the activity of the channel with gadolinium or lanthanum blocks the calcium increases and promotes cell survival. The protein target was able to overcome cell adhesion-mediated drug resistance, which often limits the usefulness of other targets. This protein is expressed in other immortalized cell lines, but has limited expression in normal native cell types in humans. Such limited expression would reduce the likelihood of adverse side effects associated with the targeting of this protein.

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The present invention concerns a novel &#x3b1;7 nicotinic receptor subunit isoform, &#x3b1;7-2. The &#x3b1;7-2 isoform contributes to novel acetylcholine receptors (AChRs) with pharmacological and biophysical properties distinct from those of wild-type &#x3b1;7-1-nAChRs and closely resembling those of &#x3b1;7-nAChRs found in intrinsic cardiac neurons and Type II &#x3b1;7-nAChRs of superior cervical ganglion neurons. Polynucleotides encoding the &#x3b1;7-2 isoform, vectors and genetically modified cells containing such polynucleotides are also provided. In addition, methods are provided for producing the &#x3b1;7-2 isoform as are methods of using such isoforms for screening compounds for activity at the nAChR.

Nucleic acids encoding functional splice variants of the &#x3b1;7 nicotinic acetylcholine receptor subunit and methods for producing the encoded proteins

Growing community of inventors

Lutz, FL, United States of America

Javier Cuevas