Methods and compositions for treatment of ocular fibrosis

A glaucoma treatment, biological technology, applied in the direction of chemical instruments and methods, biochemical equipment and methods, drug combinations, etc., can solve problems such as failure

Inactive Publication Date: 2012-10-03
GILEAD BIOLOGICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

1 / 3 to 1 / 2 trabeculectomy ultimately fails due to intraconjunctival fibrosis

Method used

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  • Methods and compositions for treatment of ocular fibrosis
  • Methods and compositions for treatment of ocular fibrosis
  • Methods and compositions for treatment of ocular fibrosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0188] Example 1: Rabbit Trabeculectomy Model

[0189] Four female New Zealand rabbits, 12-14 weeks old, weighing 2-3 kg each, were used in this study. Intramuscular injection of 55.5mg Ketalar (50mg / ml) and 39.5mg Rompun (2%) induced general anesthesia. Trabeculectomy was performed in both eyes of each animal as follows. Under the microscope, the edge-based conjunctival flap is lifted, and the subconjunctival space is bluntly dissected. After forming a scleral flap of approximately 2.5mmx4mm, a piece of trabecular meshwork was removed and iridectomy was performed. After iridectomy, the scleral and conjunctival flaps are closed. After the operation, a filtering bleb is formed.

[0190] Animals were examined and IOP was determined at defined time points post-surgery. Both eyes were examined on the first day after surgery and then every two days until the mice were sacrificed. Use the Tono-Pen A tonometer measures IOP. The size and characteristics of the bleb were o...

Embodiment 2

[0193] Example 2: IOP Determination

[0194] Intraocular pressure (IOP) was measured before trabeculectomy, on the first day after trabeculectomy, and every two days thereafter ( figure 1 ). In both left and right eyes, IOP decreased by 30-40% within 1 day after trabeculectomy and remained stable until day 13-15; IOP then increased, returning to levels comparable to or higher than those present before surgery Level.

Embodiment 3

[0195] Embodiment 3: the mensuration of filtration bleb area

[0196] Measure the length and width of the filtration bleb with a caliper to determine the area of ​​the filtration bleb ( figure 2 ). For both eyes, the mean bleb area was 14-19mm on day 1 after surgery 2 . Thereafter, the area of ​​the filtering bleb decreased steadily until the area of ​​the filtering bleb was 1-2 mm on the 13th day after trabeculectomy 2 . After 13 days, the filtering bleb failed (ie flattened, scarred and vascularized) in the two remaining animals in the study.

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Abstract

Disclosed herein are methods and compositions for treatment of ocular fibrosis, as occurs, for example, during the treatment of glaucoma by trabeculectomy. Compositions comprise modulators of the activity of one or more lysyl oxidase-type enzymes (e.g., LOX, LOXL2), and the methods include methods for making the modulators and methods for administration of the modulators to a subject in need thereof.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Patent Application Serial No. 61 / 277,918, filed September 29, 2009, and U.S. Provisional Patent Application Serial No. 61 / 397,456, filed June 11, 2010, the disclosures of which are incorporated herein by reference in their entirety for all purposes. [0003] A note about federal funding [0004] none. technical field [0005] This application is in the field of ocular neuropathies, such as occur in glaucoma, and their treatment. Background technique [0006] Glaucoma is a group of neurological eye diseases characterized by increased intraocular pressure (IOP) and optic nerve damage. Glaucoma can cause vision loss or loss and is the second leading cause of blindness. Current treatment for glaucoma involves lowering intraocular pressure by chemical or mechanical means. [0007] For example, the most common and effective treatment for glaucoma is trabeculectomy,...

Claims

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Application Information

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Patent Type & AuthorityApplications(China)
IPC IPC(8): A61K31/395A61K39/00
CPCA61K31/7088C07K16/40A61K2039/505C07K2317/76A61P27/00A61P27/02A61P27/06A61P43/00A61K48/00C12N15/86C12N2750/14141
InventorI·斯托尔曼斯T·范贝尔根V·史密斯
OwnerGILEAD BIOLOGICS