Adiponectin peptidomimetics for treating ocular disorders

Abstract

Provided herein are compositions and methods for treating dry eye or an ocular disease associated with inflammation in a subject in need thereof. The therapeutic compositions comprise an adiponectin peptidomimetic compound, and a pharmaceutically acceptable carrier, and administering a therapeutic agent. Also provided are methods for alleviating one or more symptoms or clinical signs of dry eye or an ocular disease associated with inflammation in a subject in need thereof.

What is claimed is: 
     
         1 . A method for treating dry eye in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition comprising: an adiponectin peptidomimetic compound and a Lifitegrast and a pharmaceutically acceptable carrier, to treat dry eye in the subject. 
     
     
         2 . The method of  claim 1 , wherein the composition and therapeutic agent are administered topically, by intravitreal injection, by subconjunctival injection, by conjunctival injection, by intramuscular injection, by subcutaneous injection, by intravenous injection, by intracameral injection, or by implantation into the subject's eye. 
     
     
         3 . The method of  claim 1 , wherein the dry eye is selected from the group consisting of hypolacrimation, tear deficiency, xerophthalmia, Sjogren's syndrome dry eye, non-Sjogren's syndrome dry eye, keratoconjuctivitis sicca, aqueous tear-deficiency dry eye (ADDE), evaporative dry eye (EDE), environmental dry eye, Stevens-Johnson syndrome, ocular pemphigoid blepharitis marginal, eyelid-closure failure, sensory nerve paralysis, allergic conjunctivitis-associated dry eye, post-viral conjunctivitis dry eye, post-cataract surgery dry eye, VDT operation-associated dry eye, and contact lens wearing-associated dry eye. 
     
     
         4 . The method of  claim 1 , wherein the composition is administered to the subject once a day, two times a day, three times a day, four time a day or more often. 
     
     
         5 . The method of  claim 1 , wherein the therapeutic agent is administered to the subject once a day, two times a day, three times a day, four time a day or more often. 
     
     
         6 . The method of  claim 1 , wherein the composition is administered every other day or less often. 
     
     
         7 . The method of  claim 1 , wherein the therapeutic agent is administered every other day or less often. 
     
     
         8 . The method of  claim 1 , wherein the adiponectin peptidomimetic compound is present in an amount between about 0.0001% (wt) to about 90% (wt) of the final composition. 
     
     
         9 . The method of  claim 1 , wherein the therapeutic agent is administered in an amount between about 0.1% (wt) to about 20% (wt) of the final composition. 
     
     
         10 . The method of  claim 1 , wherein the composition is in a formulation selected from the group consisting of a solution, suspension, syrup, liquid, gel, hydrogel, emulsion, liposome, aerosol, mist, film, suspension, plug, polymer, implant, contact lens, ocular insert, nanoparticle, microparticle, a sustained release formulation, and a formulation suitable for an ocular medical device. 
     
     
         11 . The method of  claim 1 , further comprising administering a composition comprising cyclosporine, artificial tears, a corticosteroid, an anti-inflammatory agent, or any combination thereof. 
     
     
         12 . The method of  claim 1 , wherein the adiponectin peptidomimetic compound is represented by Formula II:
   Xaai-Ile-Pro-Xaa 2 -Leu-Tyr-Xaa 3 -Phe-Ala-Xaa 4 -Xaa 5 (SEQ ID NO:2)  (II);
   wherein the C-terminal amino acid is optionally amidated; a variant thereof, derivative thereof, or a pharmaceutically acceptable salt thereof.   
     
     
         13 . The method of  claim 12 , wherein the adiponectin peptidomimetic compound is selected from the group consisting of D-Asn-Ile-Pro-Nva-Leu-Tyr-D-Ser-Phe-Ala-D-Ser (SEQ ID NO:3), D-Asn-Ile-Pro-Nva-Leu-Tyr-D-Ser-Phe-Ala-D-Ser-p-Ala (SEQ ID NO:4), D-Asn-Ile-Pro-Nva-Leu-Tyr-D-Ser-Phe-Ala-D-Ser-p-Ala-NH 2 (SEQ ID NO:5), D-Asn-Ile-Pro-Nva-Leu-Tyr-D-Ser-Phe-Ala-D-Ser-NH 2  (SEQ ID NO:6), (D-Asn-Ile-Pro-Nva-Leu-Tyr-D-Ser-Phe-Ala-D-Ser-His-Pro) 2 -Dab-NH 2 (SEQ ID NO:7), a variant thereof, a derivative thereof, and a pharmaceutically acceptable salt thereof. 
     
     
         14 . The method of  claim 12 , wherein the adiponectin peptidomimetic compound is SEQ ID NO:6. 
     
     
         15 . The method of  claim 1 , wherein the therapeutic agent is selected from Lifitegrast and Restasis® or a pharmaceutically acceptable salt thereof. 
     
     
         16 . The method of  claim 15 , wherein the therapeutic agent comprises about 3.5% to about 6.5% Lifitegrast or a pharmaceutically acceptable salt thereof. 
     
     
         17 . A method for treating an ocular disease associated with inflammation in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition comprising an adiponectin peptidomimetic compound of  claim 14  or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, and administering a therapeutic agent to treat the ocular disease associated with inflammation in the subject. 
     
     
         18 . A method for alleviating at least one symptom or clinical sign of dry eye in a subject in need thereof, the method comprising:
 a) administering to the subject a therapeutically effective amount of an adiponectin peptidomimetic compound of  claim 14  or a pharmaceutically acceptable salt thereof and   b) a pharmaceutically acceptable carrier; and   c) administering a therapeutic agent   to alleviate at least one symptom or clinical sign of dry eye in the subject.   
     
     
         19 . A method for treating an ocular disease or disorder in a subject in need thereof, the method comprising:
 a) administering to the subject a therapeutically effective amount of an adiponectin peptidomimetic compound of  claim 14  or a pharmaceutically acceptable salt thereof; and   b) a pharmaceutically acceptable carrier; and   c) administering a therapeutic agent to treat the ocular disease associated with inflammation in the subject.   
     
     
         20 . The method of  claim 1 , wherein the subject presents at least one symptom or clinical sign of dry eye selected from the group consisting of a change in tear secretion, a change in tear clearance, ocular surface damage, corneal epithelial defects, a change in ocular surface cells, a change in tear film stability, a change in tear volume, a change in tear film composition, a change in tear osmolarity, and any combination thereof.