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Compositions and methods for treatment of neovascular diseases

A technology of neovascularization and composition, which is applied in the field of treatment of neovascular diseases and can solve problems such as increased effects

Inactive Publication Date: 2007-11-07
THE SCRIPPS RES INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

To further complicate matters, blockade of a single pathway may also induce increased action of compensatory and other angiogenic pathways

Method used

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  • Compositions and methods for treatment of neovascular diseases
  • Compositions and methods for treatment of neovascular diseases
  • Compositions and methods for treatment of neovascular diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0125] Example 1. Treatment of neonatal mouse eyes with a combination of peptide mimetic integrin signaling inhibitors and VEGF signaling inhibitors

[0126] Following the general procedure for the angiogenesis assay described above ("General Procedure"), on postnatal day 8 (P8), neonatal Balb / C mouse eyes were injected intravitreal at a concentration of 0.25x the integrin signaling inhibitor compound (1 ) (5 mice), VEGF aptamer compound (2) at a concentration of 0.5x (5 mice), or a combination of compound (1) at a concentration of 0.25x and compound (2) at a concentration of 0.5x (6 mice ). As a control, another group of 6 mice received intravitreal injection of PBS only. Following the general protocol, mice were euthanized at P12 and retinas were removed from injected eyes, stained, mounted and evaluated microscopically. Vascularity in the second (external retinal vessels) layer was assessed based on the percentage of vascularization compared to control eyes. The results ...

Embodiment 2

[0128] Example 2. Treatment of Neonatal Mouse Eyes with Combinations of TrpRS Angiogenesis Inhibitory Fragments and VEGF Signaling Inhibitors

[0129] According to the general method, at P4, neonatal Balb / C mouse eyes were intravitreally injected with 0.1x concentration of T2-TrpRS (8 mice), 0.1x concentration of VEGF aptamer compound (2) (8 mice) or Combination of T2-TrpRS at 0.1x concentration and Compound (2) at 0.1x concentration (10 mice). As a control, another group of 8 mice received only intravitreal injection of PBS. Following the general protocol, mice were euthanized at P12 and retinas were removed from injected eyes, stained, mounted and evaluated microscopically. Vascularity in the second (external retinal vessels) layer was assessed based on the percentage of vascularization compared to control eyes. The results are shown in Table 2 and Fig. 6, Fig. 7, Fig. 8 and Fig. 9.

[0130] % suppression:

Embodiment 3

[0131] Example 3. Treatment of Neonatal Mouse Eyes with Combinations of TrpRS Angiogenesis Inhibitory Fragments and VEGF Signaling Inhibitors

[0132] According to the general method, at P4, the eyes of neonatal Balb / C mice were intravitreally injected with 1x concentration of T2-TrpRS (8 mice), 1x concentration of VEGF aptamer compound (2) (8 mice) or 1x concentration Combination of T2-TrpRS and compound (2) at 1x concentration (10 mice). As a control, another group of 6 mice received intravitreal injection of PBS only. Following the general protocol, mice were euthanized at P12 and retinas were removed from injected eyes, stained, mounted and evaluated microscopically. Vascularity in the second (external retinal vessels) layer was assessed based on the percentage of vascularization compared to control eyes. The results are shown in Table 3 and Figure 10, Figure 11, Figure 12 and Figure 13.

[0133] % suppression:

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Abstract

The present invention provides compositions and methods of treating neovascular diseases, such as a retinal neovascular diseases and tumors, by administering to a patient suffering from a neovascular disease or tumor a vascular development inhibiting amount of a combination of the angiogenesis suppressing drugs comprising an angiostatic fragment of tryptophanyl-tRNA synthetase (TrpRS) and at least one compound selected from the group consisting of a vascular endothelial growth factor (VEGF) signaling inhibitor and an integrin signaling inhibitor. Compositions for use in the methods include an admixture of an angiostatic fragment of tryptophanyl-tRNA synthetase (TrpRS) and at least one of a vascular endothelial growth factor (VEGF) signaling inhibitor and an integrin signaling inhibitor, together with a pharmaceutically acceptable excipient.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Patent Application Serial No. 60 / 577,156, filed June 4, 2004, and claims the benefit of U.S. Provisional Patent Application Serial No. 60 / 585,273, filed July 1, 2004, and also claims the The benefit of US Provisional Patent Application Serial No. 60 / 655,801 filed February 24, 2005, which is hereby incorporated by reference. [0003] Statement of Government Rights [0004] Portions of the work described in this article were supported by grant number EY11254 from the National Institutes of Health. The US Government has certain rights in this invention. field of invention [0005] The present invention relates to the treatment of neovascular diseases, such as retinal neovascular diseases. More particularly, the present invention relates to methods of treating neovascular diseases by administering to a patient a combination of angiostatic and anti-angiogenic drugs, a...

Claims

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Application Information

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IPC IPC(8): A61K31/70A01N43/04C07K1/00C07K14/00C07K17/00
Inventor M·弗里兰德H·E·阿吉拉M·I·多雷尔
Owner THE SCRIPPS RES INST
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