Methods and compositions for treatment of retinal degeneration
Inventors
Case, Casey C. • Kawanishi, Toru • Kuno, Noriyuki
Assignees
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Publication Number
US-9855299-B2
Publication Date
2018-01-02
Expiration Date
Abstract
Disclosed herein axe methods and compositions for treating retinal degeneration, such as occurs in retinitis pigmentosa and age-related macular degeneration, using descendents of marrow adherent stem cells that have been engineered to express an exogenous Notch intracellular domain.
Core Innovation
The described invention relates to treating retinal degeneration, including retinitis pigmentosa and age-related macular degeneration, by administering SB623 cells. SB623 cells are described as marrow adherent stem cells (MASCs) that are engineered to express an exogenous Notch intracellular domain (Notch NICD). The approach is directed to photoreceptor activity, photoreceptor function, and visual signal transmission associated with the retina-to-visual cortex pathway.
The disclosed methods include administration of the SB623 cells to the eye, including intravitreal transplantation or subretinal transplantation. The overall concept is that engineered MASCs expressing an exogenous Notch NICD are used in the subject to achieve improved retinal functional outcomes.
Preclinical evidence in an RCS rat model is described as showing that SB623 preserves retinal function long-term. The summary reports retained electroretinography (ERG) a-/b-waves, sustained azide responses, preserved outer nuclear layer (ONL) histology, and preserved visually evoked potentials (VEP), indicating maintained retina-to-visual cortex signal transmission.
Claims Coverage
The document provides three independent claims covering increasing electrical activity of a photoreceptor cell, preventing loss of outer nuclear layer cells, and enhancing transmission of visual signals from the retina to the visual cortex. The common inventive feature is cells descended from marrow adherent stem cells (MASCs) engineered to express an exogenous Notch intracellular domain.
Administering MASCs expressing an exogenous Notch intracellular domain to increase photoreceptor electrical activity
A method for increasing electrical activity of a photoreceptor cell in a subject by administering cells descended from marrow adherent stem cells (MASCs) engineered to express an exogenous Notch intracellular domain.
Administering MASCs expressing an exogenous Notch intracellular domain to prevent outer nuclear layer cell loss
A method for preventing loss of cells of the outer nuclear layer of the retina in a subject by administering cells descended from marrow adherent stem cells (MASCs) engineered to express an exogenous Notch intracellular domain.
Administering MASCs expressing an exogenous Notch intracellular domain to enhance retina-to-visual cortex signal transmission
A method for enhancing transmission of visual signals from the retina to the visual cortex in a subject by administering cells descended from marrow adherent stem cells (MASCs) engineered to express an exogenous Notch intracellular domain.
The claims cover engineered MASCs expressing an exogenous Notch intracellular domain used to increase photoreceptor electrical activity, prevent outer nuclear layer cell loss, and enhance transmission of visual signals from the retina to the visual cortex. Dependent claims refine delivery by transplantation into the eye, including intravitreal or subretinal routes, and specify retinitis pigmentosa and age-related macular degeneration (AMD).
Stated Advantages
Preserves retinal function long-term in an RCS rat model.
Retains electroretinography (ERG) a-/b-waves.
Maintains sustained azide responses.
Preserves outer nuclear layer (ONL) histology.
Preserves visually evoked potentials (VEP), indicating maintained retina-to-visual cortex signal transmission.
Documented Applications
Treating retinal degeneration, including retinitis pigmentosa and age-related macular degeneration, in a subject by administering engineered MASCs (SB623) expressing an exogenous Notch intracellular domain.
Increasing photoreceptor electrical activity in a subject.
Preventing loss of cells of the outer nuclear layer of the retina in a subject.
Enhancing transmission of visual signals from the retina to the visual cortex in a subject.
Potential intravitreal or subretinal transplantation into the eye as an administration route for the engineered cells.
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