Methods and compositions for treating Huntington's disease

• US 10,369,201 B2
• Filed: 11/11/2014
• Issued: 08/06/2019
• Est. Priority Date: 11/11/2013
• Status: Active Grant

• Current Assignee: Sangamo Therapeutics, Inc.
• Original Assignee: Sangamo Therapeutics, Inc.
• Inventors: Zhang, H. Steve
• Primary Examiner(s): Noble, Marcia S
• Application Number:
  US15/036,020
• Publication Number:
  US 20160296605A1
• Time in Patent Office: 1,729 Days
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/164 from bacteria
• CPC Class Codes: A61K 38/465 acting on ester bonds (3.1), e.g. lipases, ribonucleases
• 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: A61K 9/0085 Brain, e.g. brain implants; Spinal cord
• 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: C12N 15/113 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 Class Codes: C12N 2310/10 Type of nucleic acid
• CPC Class Codes: C12N 2310/20 involving clustered regularly interspaced short palindromic repeats [CRISPRs]
• CPC Class Codes: C12N 2320/34 Allele or polymorphism specific uses
• CPC Class Codes: C12N 2750/14143 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00
• CPC Class Codes: C12Y 301/00 Hydrolases acting on ester bonds (3.1)

Abstract

Disclosed herein are methods and compositions for diagnosing, treating or preventing Huntington'"'"'s Disease.

Claims

1. A method of increasing levels of at least two of PDE10a, DARPP-32, DRD1 and DRD2 in a medium spiny neuron (MSN) of a mouse or human subject, the method comprising administering to the striatum of the subject a genetic repressor comprising a polynucleotide encoding a zinc finger protein DNA-binding protein (ZFP) comprising 3 to 6 zinc finger domains comprising the recognition helix regions in the order shown in a single row of Table 1B, which ZFP binds to a target sequence as shown in Table 2B, wherein the repressor represses transcription of a mutant Huntingtin (Htt) gene, thereby increasing levels of at least two of PDE10a, DARPP-32, DRD1 and DRD2 in the subject at least 30% as compared to a control subject which was not administered the genetic repressor.

2. The method of claim 1, wherein the PDE10a, DARPP-32, DRD1 and/or DRD2 levels are increased at least 40% or 50% or more relative to the control.

3. The method of claim 1, wherein the DNA-binding domain is fused to a functional domain.

4. The method of claim 3, wherein the functional domain is a transcriptional repression domain or a nuclease.

5. The method of claim 1, wherein the genetic repressor is administered using a viral or non-viral vector.

6. The method of claim 5, wherein the non-viral vector is an adeno-associated virus (AAV) vector.

7. A method of treating Huntington'"'"'s Disease in a mouse or human subject with a mutant Htt gene, the method comprising increasing levels of at least two of PDE10a, DARPP-32, DRD1 and DRD2 in a medium spiny neuron (MSN) according to the method of claim 1.

8. The method of claim 1, wherein levels of at least three of PDE10a, DARPP-32, DRD1 and DRD2 are increased.

9. The method of claim 8, wherein levels of PDE10a, DARPP-32, DRD1 and DRD2 are increased.