Methods of treating optic nerve diseases using neural progenitor cell growth factors
Inventors
BERNSTEIN, Steven Lance • KERR, Candace L. • TEMPLE STERN, Sally
Assignees
University of Maryland Baltimore • REGENERATIVE RES FOUNDATION
Publication Number
US-12213996-B2
Publication Date
2025-02-04
Expiration Date
2039-02-01
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Abstract
Optic nerve lamina region neural progenitor cells (ONLR-NPCs) are provided. Such cells secrete growth factors and survival factors that can be used in the treatment of optic nerve diseases, such as glaucoma. Also provided are methods of treating or preventing optic nerve diseases, such as glaucoma, using one or more factors secreted by ONLR-NPCs, combinations of factors secreted by ONLR-NPCs, or culture media conditioned by ONLR-NPCs.
Core Innovation
The invention provides optic nerve lamina region neural progenitor cells (ONLR-NPCs), which are characterized as cells located in the optic nerve lamina region of the eye and defined by specific marker proteins, such as nestin(+), SOX2(+), GFAP(+), and NG2(−). These ONLR-NPCs secrete growth and survival factors essential for maintaining ocular health and function. The patent also describes ONLR-NPC cultures, conditioned media, lysates, and extracts, as well as compositions comprising these cells or their secreted factors.
The problem addressed by the invention is the lack of effective treatments for optic nerve diseases, such as glaucoma, beyond strategies that reduce intraocular pressure. Current therapies do not adequately address the progressive degeneration of the optic nerve or loss of neurotrophic support, particularly as associated with age-related depletion of ONLR-NPCs and their secreted factors. Such depletion is linked to increased severity and progression of optic nerve diseases.
The invention introduces therapeutic methods of treating or preventing optic nerve diseases in subjects by administering a composition comprising one or more of the following: a population of ONLR-NPCs, ONLR-NPC conditioned media, ONLR-NPC lysates, ONLR-NPC extracts, or factors secreted by ONLR-NPCs, individually or in combination. These compositions can be delivered to the eye via topical application, subconjunctival, intravitreal, or retrobulbar injection, and are applicable for various optic nerve diseases including glaucoma, optic nerve hypoplasia, and optic neuritis.
Claims Coverage
The patent contains one independent claim, which covers a method of treating or preventing optic nerve disease using compositions derived from or associated with optic nerve lamina region neural progenitor cells.
Method of treating or preventing optic nerve disease using ONLR-NPC-based compositions
The invention covers a method comprising administering to a subject a therapeutically effective amount of a composition comprising one or more of: - a population of optic nerve lamina region-neural progenitor cells (ONLR-NPCs) - ONLR-NPC conditioned media - an ONLR-NPC lysate The method is for treating or preventing an optic nerve disease in the subject. Key features include: - Applicable to optic nerve diseases such as open-angle glaucoma, angle-closure glaucoma, optic nerve hypoplasia, optic nerve hypomyelination, regional axonal dysfunction, nonarteritic anterior ischemic optic neuropathy (NAION), and optic neuritis. - Compositions can be administered to the eye via topical application, subconjunctival injection, intravitreal injection, or retrobulbar injection. - ONLR-NPCs are characterized by expression of markers such as nestin(+), SOX2(+), GFAP(+), NG2(−) and may further express SOX1(+), vimentin(+), BDNF(+). - Compositions can also include factors secreted by ONLR-NPCs, such as Latent Transforming Growth Factor-Beta 1 (TGF-β1), Connective Tissue Growth Factor (CTGF), Nerve Growth Factor (NGF), Fibroblast Growth Factor (FGF-1), Vascular Endothelial Growth Factor (VEGF), Mesenchymal Astrocyte Neurotrophic Factor (MANF), and Insulin-like Growth Factors-1 and -2 (IGF-1 and IGF-2), as well as other specified growth factors and proteins.
The claims broadly cover methods for treating or preventing optic nerve diseases by administering ONLR-NPCs or related compositions, including their conditioned media, lysates, or secreted factors, with specified markers and growth factor profiles.
Stated Advantages
The invention addresses unmet needs for alternative or supplemental treatments for optic nerve diseases, particularly glaucoma, beyond intraocular pressure reduction.
Replacement of growth and survival factors secreted by ONLR-NPCs may improve the treatment and prevention of optic nerve diseases.
Methods using ONLR-NPC-derived compositions can potentially restore or support glial cell growth, myelination, and enable glial replacement and remyelination in the optic nerve.
Therapies based on ONLR-NPCs and their secreted factors may counteract age-related loss of neurotrophic support and progressive optic nerve degeneration.
Documented Applications
Treatment or prevention of open-angle glaucoma and angle-closure glaucoma.
Treatment or prevention of optic nerve hypoplasia, optic nerve hypomyelination, and regional axonal dysfunction.
Treatment or prevention of nonarteritic anterior ischemic optic neuropathy (NAION) and optic neuritis.
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