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Compositions and methods for treating ocular pathologies

An eye and drug technology, applied in chemical instruments and methods, drug combinations, active ingredients of heterocyclic compounds, etc.

Pending Publication Date: 2020-01-07
BOARD OF SUPERVISORS OF LOUISIANA STATE UNIV & AGRI & MECHANICAL COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in certain tissues and diseases such as the eye, dysregulation of these tightly controlled processes can lead to angiogenesis-mediated pathological conditions

Method used

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  • Compositions and methods for treating ocular pathologies
  • Compositions and methods for treating ocular pathologies
  • Compositions and methods for treating ocular pathologies

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0178] Example 1. Treatment of herpetic keratitis

[0179] Serotonin or 5-hydroxytryptamine (5-HT) is a small monoamine molecule known primarily for its role as a neurotransmitter. 5-HT regulates a variety of behaviors in the brain, including cognition, mood, aggression, mating, feeding, and sleep (Nichols and Nichols, 2008). These actions are mediated through seven different receptor families (5-HT 1-7 ), these families contain fourteen distinct subtypes (Nichols and Nichols, 2008). Except 5-HT 3 Receptors are ligand-gated ion channels, each of which is a G protein-coupled receptor. Of all the serotonin receptors, 5-HT is known to couple mainly to the Gαq effector pathway 2A The receptor (Roth et al., 1986) is the one most closely related to complex behavior.

[0180] Agonists of the serotonin receptor pathway, such as DOIs, can be delivered systemically or locally (eg, by topical eye drops) to prevent and abrogate pathogen-selected host-mediated disease processes. Such...

Embodiment 2

[0186] Example 2: Development of preclinical models

[0187] The data presented above demonstrate that DOI can effectively inhibit disease-associated ocular vascularization, thereby preventing the chronic pathology often associated with disease progression. Without wishing to be bound by theory, DOIs may regulate angiogenesis and vascular homeostasis in these disease processes through direct or indirect effects on vascular cells.

[0188] To assess the effect of DOI on ocular herpetic stromal keratitis associated with pathological angiogenesis, other animal model systems can be developed as described herein. The model system described can be complemented by established in vitro mechanistic studies to assess the direct effects of DOIs on vascular cell biology and function. The contribution of 5-HT receptors in this disease process can likewise be explored.

[0189] Assessing therapeutic efficacy of 5-HT receptor modulation for ameliorating pathological conditions associated w...

Embodiment 3

[0195] Example 3: Formulation Development and Validation

[0196] Aspects of the invention are directed to DOI, a 5-HT that can treat herpetic keratitis 2 R agonist. In the study, (R)-DOI exhibited anti-angiogenic properties in mouse models of primary and chronic herpetic keratitis. Furthermore, (R)-DOI inhibited HSV-1 reactivation from latency in an isolated neuronal model, a major factor in the development of recurrent herpetic stromal keratitis. Without wishing to be bound by theory, the experiments described herein (i) demonstrate that (R)-DOI improves blood vessel formation associated with herpetic keratitis, (ii) develop formulations and methods for effective (R)-DOI ophthalmic delivery. Dosing parameters, and (iii) a CNS safety profile for ophthalmic (R)-DOI was established.

[0197] Tolerability and Pharmacokinetic Parameters of Ophthalmic Preparations of (R)-DOI

[0198] A series of experiments aimed at determining the dosing parameters, including ocular tolerab...

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Abstract

The invention features compositions, methods, and kits for treating conditions associated with pathological ocular neovascularization, reducing scarring in the eye, treating dry eye, treating maculardegeneration, and treating keratitis by administering a serotonin receptor agonist.

Description

[0001] This application claims priority to US Provisional Application No. 62 / 492,841, filed May 1, 2017, the contents of which are incorporated herein by reference in their entirety. [0002] All patents, patent applications, and publications cited herein are hereby incorporated by reference in their entirety. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art known to those skilled in the art as of the date of the invention described and claimed herein. [0003] This patent disclosure contains material that is protected by copyright. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure as it appears in the USPTO patent files or records, but otherwise reserves any and all copyrights thereto. [0004] Statement Regarding Federally Funded Research [0005] This invention was made with Gover...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K45/06A61P27/02C07K14/705
CPCA61K45/06A61P27/02C07K14/70571A61K31/404A61K31/4045A61K31/4439A61K31/48A61K31/522A61K31/7072A61K2300/00A61K31/137A61K9/0048A61K9/06
Inventor T·P·福斯特C·D·尼克尔斯
Owner BOARD OF SUPERVISORS OF LOUISIANA STATE UNIV & AGRI & MECHANICAL COLLEGE
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