Stable neural stem cells comprising an exogenous polynucleotide coding for a growth factor and methods of use thereof

• US 9,750,769 B2
• Filed: 10/19/2015
• Issued: 09/05/2017
• Est. Priority Date: 10/20/2014
• Status: Active Grant

• Current Assignee: Neuralstem Incorporated (City of Tianjin (China))
• Original Assignee: Neuralstem Incorporated (City of Tianjin (China))
• Inventors: Hazel, Thomas, Johe, Karl K.
• Primary Examiner(s): Hayes, Robert C
• Application Number:
  US14/886,272
• Publication Number:
  US 20160120942A1
• Time in Patent Office: 687 Days
• Field of Search: None
• CPC Class Codes: A61K 35/30 Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• CPC Class Codes: A61K 38/30 Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 insulin-like growth factor binding protein A61K38/1754
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C07K 14/65 Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
• CPC Class Codes: C12N 5/0618 Cells of the nervous system
• CPC Class Codes: C12N 5/0623 Stem cells
• CPC Class Codes: C12N 5/10 Cells modified by introduction of foreign genetic material

Abstract

The present disclosure provides a human neural stem cell comprising an exogenous polynucleotide coding for a growth factor such as IGF-1. Also disclosed are methods of using the human neural stem cells for the treatment of neurodegenerative diseases or disorders including, for example, ALS.

Claims

1. A human neural stem cell comprising a vector containing an exogenous polynucleotide coding for insulin-like growth factor 1 (IGF-1), wherein IGF-1 comprises a nucleotide sequence as set forth in SEQ ID NO:

1, and wherein the IGF-1 nucleotide sequence is stably expressed, and wherein the human neural stem cell is expandable for more than sixty cell doublings without undergoing differentiation.

2. The human neural stem cell of claim 1, wherein the exogenous polynucleotide coding for IGF-1 is operably linked to a ubiquitin C (UbC) promoter, a human phosphoglycerate kinase 1 promoter, a human synapsin promoter, or a synthetic CAG promoter.

3. The human neural stem cell of claim 1, wherein the stem cell differentiates into a significantly increased number of GAD65-positive GABAergic neurons compared to a neural stem cell that does not comprise an exogenous polynucleotide coding for IGF-1.

4. The human neural stem cell of claim 1, wherein the human neural stem cell is obtained from a fetus or an embryo.

5. The human neural stem cell of claim 4, wherein the human neural stem cell is obtained from a fetus having a gestational age of about 5 to about 20 weeks.