GLAUCOMA TREATMENT

• US 20150366953A1
• Filed: 02/12/2014
• Published: 12/24/2015
• Est. Priority Date: 02/13/2013
• Status: Active Grant

• Current Assignee: Icahn School of Medicine at Mount Sinai, The Research Foundation for The State University of New York (State University of New York)
• Original Assignee: Icahn School of Medicine at Mount Sinai, The Research Foundation for The State University of New York (State University of New York)
• Inventors: DANIAS, John, CANDIA, Oscar A., GEROMETTA, Rosana
• Granted Patent: US 10,946,076 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/09 having two or more such linkages
• CPC Class Codes: A61K 31/12 Ketones
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 38/204 IL-6
• CPC Class Codes: A61K 38/49 Urokinase; Tissue plasminogen activator
• 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 27/06 Antiglaucoma agents or miotics
• 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 15/86 Viral vectors
• CPC Class Codes: C12N 2310/141 MicroRNAs, miRNAs
• CPC Class Codes: C12N 2710/10341 Use of virus, viral particle or viral elements as a vector
• CPC Class Codes: C12N 2740/15043 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2740/15071 Demonstrated in vivo effect
• CPC Class Codes: C12N 2750/00043 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2750/00071 Demonstrated in vivo effect
• 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 304/21068 Tissue plasminogen activator (3.4.21.68), i.e. tPA

Abstract

Disclosed herein are methods of treatment for an intraocular pressure (IOP)-associated condition in a subject, that include administering to the subject an effective amount of a tissue plasminogen activator (tPA) therapeutic agent. In one embodiment, the IOP-associated condition is glaucoma. The administration of a tPA therapeutic agent can be an extended administration intended to cause a reduction in IOP in the subject for a period of at least one day to a year or more, relative to IOP levels in the subject prior to administration of the tPA therapeutic agent. The tPA therapeutic agent can be, for example, tPA, a tPA derivative, a small molecule direct or indirect tPA agonist, or a gene therapy vector.

Claims

1. A method of treatment for an intraocular pressure (IOP)-associated condition in a subject, comprising administering to said subject an effective amount of a tissue plasminogen activator (tPA) therapeutic agent.

2. The method of claim 1, wherein the administration comprises recurrent administration of said tPA therapeutic agent.

3. The method of claim 1 or 2, wherein administration of the tPA therapeutic agent reduces IOP in said subject for a period of at least one day to a year or more, relative to IOP measurements in said subject prior to administration of the tPA therapeutic agent.

4. The method of claim 2, wherein the administration comprises administering the tPA therapeutic agent to said subject for a period of at least two weeks.

5. The method of any of claims 1-4, wherein the tPA therapeutic agent is selected from the group consisting of:

tPA;

a tPA variant, functional derivative, or homolog;

a small molecule tPA agonist;

an RNA molecule that causes tPA upregulation;

a polypeptide that causes tPA upregulation;

an RNA molecule or other agent that down-regulates a negative regulator of tPA expression or activity; and

a gene therapy vector.

6. The method of claim 5, wherein the tPA therapeutic agent is a small molecule tPA agonist, or an analog of a small molecule tPA agonist, said small molecule tPA agonist being selected from the group consisting of:

an oxysterol, N-acetyl-cysteine, Neovastat, nicotine, allopregnanolone, testosterone, forskolin, L-threo-DOPS, PACAP, a PDE4 activator, 5-azacytidine, CPT-cAMP, retinoic acid, a phorbol ester, 8-bromo-cAMP, 2-diocynoyl-sn-glycerol (diC8), Phorbol 12 myristate 13 acetate (PMA), AF12198, CE3F4, Prostaglandin E2 (PGE2), Butyrate, 1,25-dihydroxyvitamin D-3, estradiol, an estrogen analogue, laminin, Interleukin-6 (IL-6), ascorbic acid, sesamol, and lysophosphatidylcholine.

7. The method of claim 5, wherein the tPA therapeutic agent is a tPA gene therapy vector comprising a nucleic acid sequence encoding:

tPA;

a tPA variant, functional derivative or homolog;

a polypeptide or molecule that causes up-regulation of tPA expression;

or a polypeptide or molecule that causes down-regulation of a negative regulator of tPA expression.

8. The method of claim 5, wherein the tPA therapeutic agent is an RNA molecule or other tPA therapeutic agent that down-regulates a negative regulator of tPA expression or activity.

9. The method of claim 5, wherein said gene therapy vector is a lentivirus or adeno-associated virus (AAV)-based vector.

10. The method of any of claims 1-9, wherein said subject has glaucoma.

11. The method of any of claims 1-10, wherein the tPA therapeutic agent is administered topically, systemically, by injection, by iontophoresis, or by implantation of cells that produce said tPA therapeutic agent.

12. The method of any of claims 1-11, wherein the tPA therapeutic agent is administered at dosages of 10-120 μ

l per dose.

13. The method of any of claims 4-12, wherein the tPA therapeutic agent is administered to said subject for a period of at least one month.