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Methods for treating ocular neovascular diseases

A treatment method, new blood vessel technology, applied in treatment, electrotherapy, sensory diseases, etc., can solve problems such as high recurrence rate

Inactive Publication Date: 2005-02-16
EYETECH PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, only a subset of eyes meet eligibility criteria for this type of therapeutic intervention and those treated with this type have a high rate of relapse

Method used

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  • Methods for treating ocular neovascular diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0084] Embodiment 1: skin blood vessel permeability test (Miles test)

[0085] One of the biological activities of VEGF is to increase vascular permeability through specific binding to receptors on vascular endothelial cells. This interaction loosens the tight endothelial junction with consequent leakage of vascular fluid. Vascular leakage induced by VEGF in vivo can be determined based on Evans blue dye leaking from guinea pig vasculature as a result of percutaneous injection of VEGF (Dvorak HF, Brown LF, Detmar M, Dvorak AM. "Vascular permeability factor / vascular Endothelial growth factor, microvascular hyperpermeability and angiogenesis" - Am J Pathol. 1995, 146: 1029.) Similarly, this assay can be used to determine the ability of compounds to block this biological activity of VEGF.

[0086] VEGF 165 (20-30 nM) premixed with EYE001 (30 nM-1 μM) and then injected percutaneously into the shaved skin of the back of guinea pigs. The amount of Evans blue dye leakage around ...

Embodiment 2

[0087] Example 2: Corneal Angiogenesis Test

[0088] will contain VEGF 165 (3 pmol) of methacrylate polymer particles were implanted into the rat corneal stroma to induce blood vessel growth into normal avascular cornea. EYE001 was administered intravenously to rats at doses of 1, 3 and 10 mg / kg once or twice a day for 5 days. At the end of the treatment period, photomicrographs were taken of all individual corneas. The extent of neovascularization in corneal tissue and its inhibition by EYE001 was quantified by standardized morphometric analysis of photomicrographs.

[0089] Data (not shown) demonstrated that systemic treatment with EYE001 produced a significant inhibition (65%) of VEGF-dependent angiogenesis in the cornea compared to phosphate buffered saline (PBS). Once-daily treatment with 10 mg / kg had the same effect as twice-daily treatment. The 3 mg / kg dose had the same activity as the 10 mg / kg dose, but at 1 mg / kg there was apparently no significant efficacy.

Embodiment 3

[0090] Example 3: Research on Retinopathy of Prematurity

[0091] Although ROP is clearly distinct from diabetic retinopathy and AMD, the ROP mouse model has been used to demonstrate the role of VEGF in the abnormal retinal vascularization that occurs in this disease (Smith LE, Wesolowski E, McLellan A, Kostyk SK, Amato DR, Sullivan R, D'Amore PA. "Oxygen-induced retinopathy in mice" - Invest Ophthalmol Vis Sci. 1994, 35: 101.). These data provide a rationale for studying the anti-angiogenic effects of EYE001 in this model.

[0092] 9, 8, 8, 7 and 7 mouse litters were placed in an air chamber or hyperoxic chamber and treated intraperitoneally with PBS or EYE001 (1, 3 or 10 mg / kg day) . The end point of the experiment was evaluated by microscopically identifying and counting neovascular sprouts on 20 tissue sections from each eye of all treated and control mice, i.e. neocapillaries passing through the inner limiting membrane of the retina into the vitreous humor. Vascular ...

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Abstract

Disclosed herein are methods for treating ocular neovascular disease using anti-VEGF therapy in combination with a second therapy that inhibits the development of ocular neovascularization or destroys abnormal blood vessels in the eye, such as photodynamic therapy.

Description

field of invention [0001] The present invention relates to methods of treating ocular neovascularization using agents that inhibit VEGF. Background of the invention [0002] Angiogenesis, or abnormal blood vessel growth, is considered a major cause of pathological conditions in many fields of medicine including ophthalmology, cancer and rheumatology. For example, the exudative or neovascular form of age-related macular degeneration (AMD) is a leading cause of blindness in middle-aged and older adults. There is currently no standard and effective therapy for the treatment of exudative ADM in most patients. Thermal laser photocoagulation and photodynamic therapy (PDT) have proven beneficial in small groups of such patients. However, only a subset of eyes meet eligibility criteria for such therapeutic interventions and those treated with such treatments have a high rate of relapse. [0003] Recent preclinical studies have suggested that pharmacological intervention or anti-a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61FA61K31/409A61K31/70A61K31/7088A61F9/007A61K39/395A61K45/00A61K48/00A61N1/30A61P27/02A61P43/00C07HC07H21/00C12N5/10C12Q1/68
CPCA61K31/7088A61K31/555C12Q1/6886A61K31/765A61K31/409A61P27/02A61P43/00A61K31/70
Inventor 戴维·R·盖耶
Owner EYETECH PHARMA
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