Method of treating neurological disorders using long non-coding RNAs

Patent metadata

Field	Value
Publication number	US-9822359-B1
Application number	US-201514602945-A
Country	US
Kind code	B1
Filing date	Jan 22, 2015
Priority date	Jan 22, 2014
Publication date	Nov 21, 2017
Grant date	Nov 21, 2017

Abstract

A method of treating traumatic brain injury (TBI) and other neurological disorders is presented herein. Both conditioned media (CM) containing long non-coding RNAs such as NEAT1 (nuclear enriched abundant transcript 1) and MALAT1 (metastasis associated lung adenocarcinoma transcript 1) as well as human adipose-derived stem cells (hADSCs) themselves (Tx), when administered at least 3 hours post injury, were found to significantly ameliorate motor and cognitive functions in young, but not aged, mice undergoing TBI. Significant reduction in cortical damage and hippocampal cell loss was observed in both Tx and CM groups in young rats, whereas less neuroprotection was detected in the aged rats and mainly in the Tx group but not the CM group, which may in part result from decreased homing of the cells to the spleen.

First claim

What is claimed is:

1. A method of treating traumatic brain injury in a patient in need thereof comprising administering a therapeutically effective amount of long non-coding RNAs (lncRNAs) to the patient wherein the lncRNAs are nuclear enriched abundant transcript 1 (NEAT1) and metastasis associated lung adenocarcinoma transcript 1 (MALAT1), wherein the lncRNAs are administered in adipose-derived stem cells (ADSCs) lacking endothelial markers or conditioned media from cultured ADSCs.

2. The method of claim 1 , wherein the ADSCs are administered to the patient intravenously.

3. A method of improving cognition in a patient having traumatic brain injury comprising administering a therapeutically effective amount of lncRNAs to the patient wherein the lncRNAs are NEAT1 and MALAT1, wherein the lncRNAs are administered to the patient intravenously in ADSCs lacking endothelial markers or conditioned media from cultured ADSCs.

4. A method of inducing neuroprotection in a patient having a traumatic brain injury comprising administering a therapeutically effective amount of lncRNAs to the patient wherein the lncRNAs are NEAT1 and MALAT1, wherein the lncRNAs are administered in ADSCs lacking endothelial markers or conditioned media from cultured ADSCs.

5. The method of claim 4 , wherein the ADSCs are administered to the patient intravenously.

Assignees

• Cooper Denise R
• Borlongan Cesario
• Bickford Paula Cole
• Patel Niketa A
• Gould Lisa
• Univ South Florida
• Us Veterans Affairs

Inventors

• Cooper Denise R
• Borlongan Cesario
• Bickford Paula Cole
• Patel Niketa A
• Gould Lisa

Classifications

• A61K35/35

  Fat tissue; Adipocytes; Stromal cells; Connective tissues (adipose-derived stem cells A61K35/28; collagen A61K38/39) · CPC title

• C12N2310/111

  spanning the whole gene, or a large part of it · CPC title

• A61K31/7105

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• C12N15/113 Primary

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• C12N2320/32

  Special delivery means, e.g. tissue-specific · CPC title