Compounds and methods of use thereof for treating neurodegenerative disorders

Inventors

Zack, Donald J.Berlinicke, CynthiaHackler, LaszloYang, ZhiyongSteiner, Joseph P.Vojkovsky, TomasFERRARIS, DanaSlusher, Barbara S.Inglese, James

Assignees

Johns Hopkins UniversityNational Institutes of Health NIH

Publication Number

US-9382229-B2

Publication Date

2016-07-05

Expiration Date

2032-02-15

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Abstract

Compounds, compositions, kits and methods for treating conditions related to neurodegeneration or ocular disease, are disclosed.

Core Innovation

The invention provides compounds, compositions, kits and methods for treating conditions related to neurodegeneration or ocular disease. Specifically, the compounds of Formula (Ia) and Formula (I), including pharmaceutically acceptable salts thereof, are disclosed for these therapeutic purposes.

The invention addresses the problem that neurodegenerative disorders, such as glaucoma, result in neuronal cell damage leading to vision loss and blindness, especially in the elderly. Current treatments, often aimed at reducing intraocular pressure, are only partially effective and generally cannot restore neuronal cell function once lost. Moreover, neurodegenerative disorders impose significant financial burdens and have inadequate existing therapeutic options, particularly as their incidence increases with an aging population.

Claims Coverage

The independent claims focus on compounds of a specific chemical formula and their use in treating neurodegenerative diseases.

Compounds of Formula (Ia)

A compound of Formula (Ia) comprising a specific chemical structure with defined substituents R1 and R2, and pharmaceutically acceptable salts thereof.

The claims cover the chemical structure of novel compounds defined by Formula (Ia) and include pharmaceutically acceptable salts, forming the basis for therapeutic applications in neurodegenerative diseases.

Stated Advantages

The compounds, such as VX-680, promote the survival of retinal ganglion cells more potently than known compounds like sunitinib and have a wider therapeutic window.

The disclosed compounds show neuroprotective activity exceeding that of known neurotrophic factors and can prevent death of damaged neuronal cells or promote neurite growth or regeneration.

Documented Applications

Treatment or prevention of neurodegenerative diseases, disorders, or conditions, particularly ocular-related neurodegeneration such as glaucoma.

Use in promoting survival and neurite outgrowth of retinal ganglion cells and other neurons, including hippocampal neurons.

Application in treatment of various neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and related nervous system disorders.

Use in treating nervous system injuries caused by trauma, stroke, or chemical injury.

Use in culturing neuronal cells in vitro or ex vivo to prevent neuronal cell death or loss of function, including improving survival or integration of transplanted neuronal cells.

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