METHODS OF TREATING NEURODEGENERATIVE DISORDERS COMPRISING DNA METHYLTRANSFERASE INHIBITORS

• US 20190307782A1
• Filed: 06/13/2017
• Published: 10/10/2019
• Est. Priority Date: 06/13/2016
• Status: Active Grant

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Yano, Hiroko, Kim, Albert
• Granted Patent: US 10,842,807 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/706 containing six-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present disclosure provides a method of treating a neurodegenerative disorder, the method comprising administering a DNA methyltransferase inhibitor.

Claims

1. A method to reduce symptoms associated with neurodegenerative disorder in a subject, the method comprising administering to the subject a DNA methylation inhibitor.

2. A method of claim 1, wherein the neurodegenerative disorder is Huntington'"'"'s disease.

3. The method of claim 1, wherein the DNA methylation inhibitor is a nucleoside analog DNA methyltransferase (DNMT) inhibitor.

4. The method of claim 3, wherein the DNMT inhibitor is decitabine or FdCyd.

5. The method of claim 1, wherein the DNA methylation inhibitor is administered by the intracerebroventricular (icy) route.

6. The method of claim 1, wherein the DNA methylation inhibitor is administered intravenously, intramuscularly, or subcutaneously.

7. A method to reduce mutant huntingtin protein (Htt)-induced neurotoxicity, the method comprising contacting a nucleoside analog DNA methyltransferase (DNMT) inhibitor to neurons.

8. The method of claim 7, wherein the DNMT inhibitor is decitabine or FdCyd.

9. The method of claim 7, wherein the DNMT inhibitor decreases the levels of mutant Htt aggregates.

10. The method of claim 7, wherein the neurons are in vivo.

11. A method of preventing the development of the symptoms associated with neurodegenerative disorder in a subject at risk of developing the neurodegenerative disorder, the method comprising administering to the subject a DNA methylation inhibitor.

12. A method of claim 11, wherein the neurodegenerative disorder is Huntington'"'"'s disease.

13. The method of claim 11, wherein the DNA methylation inhibitor is a nucleoside analog DNA methyltransferase (DNMT) inhibitor.

15. The method of claim 11, wherein the DNA methylation inhibitor is administered by the intracerebroventricular (icy) route.

16. The method of claim 11, wherein the DNA methylation inhibitor is administered intravenously, intramuscularly, or subcutaneously.

14. The method of claim 14, wherein the DNMT inhibitor is decitabine or FdCyd.