University of South Florida

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

H. Lee Moffitt Cancer Center and Research Institute, Inc.

Shijie Song

Juan Sanchez-Ramos

Vasyl Sava

Said M Sebti

Shyam S Mohapatra

Subhra Mohapatra

Paul R Sanberg

Thomas B Freeman

William Janssen

Described herein are compound for the modulation of the G-CSF receptor. The compounds may act as agonists, antagonists, and/or mixed or partial agonists/antagonists of G-CSF. Further provided herein are methods of treating a condition, including, for example, a neurodegenerative disease, by administering a compound as detailed herein.

Small molecules that mimic or antagonize actions of granulocyte colony-stimulating-factor (G-CSF)

The compositions and methods of the disclosure particularly target the divalent metal transporter expressed on olfactory nerve terminals to transport divalent cation-coated or cation-containing nanoparticles to all regions of brain. It has been found that such divalent cation-containing nanoparticles, including those nanoparticles comprising manganese have affinity for the metal transport receptor proteins. Although this receptor has particular affinity for manganese, it is contemplated that other divalent ions, including magnesium, calcium, and the like may also be bound to such receptors leading to transport of the nanoparticles into the intracellular cytoplasm. Nanoparticles have been developed, therefore, as vehicles for parenteral delivery of genes, proteins and drugs. The present disclosure encompasses embodiments of nanoparticle-based compositions and methods for the use thereof for the delivery of genes, oligonucleotides, including but not limited to small interfering RNA, and other small molecule drugs, into the brain by nasal insufflation.

Manganese ion coated nanoparticles for delivery of compositions into the central nervous system by nasal insufflation

A method of treating neurological deficit in which the brain area affected is focally and precisely stimulated by the transient insertion and subsequent removal of a micro-needle. This insertion and subsequent removal of the micro-needle induces endogenous stem cells to proliferate, migrate and promote the brain's self-repair mechanisms. The micro-needle stimulation causes the birth of new neural cells within the brain as well as mobilizes bone marrow derived cells with a neuronal phenotype to migrate to the site of stimulation to repair and replace damaged neural cells. By repairing and/or replacing injured or dead cells, this approach will slow down the degenerative course of the disease and may result in reversal of symptoms.

Promotion of brain self-repair mechanisms by stereotaxic micro-stimulation

Bone marrow stromal cells (BMSC) differentiate into neuron-like phenotypes in vitro and in vivo, engrafted into normal or denervated rat striatum. The BMSC did not remain localized to the site of the graft, but migrated throughout the brain and integrated into specific brain regions in various architectonic patterns. The most orderly integration of BMSC was in the laminar distribution of cerebellar Purkinje cells, where the BMSC-derived cells took on the Purkinje phenotype. The BMSC exhibited site-dependent differentiation and expressed several neuronal markers including neuron-specific nuclear protein, tyrosine hydroxylase and calbindin. BMSC can be used to target specific brain nuclei in strategies of neural repair and gene therapy.

Bone marrow cells as a source of neurons for brain and spinal cord repair

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Tampa, FL, United States of America

Shijie Song