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Science

Neurotech has created genetically-engineered cell lines to produce a therapeutic protein.

 

The foundation of the Encapsulated Cell Technology (ECT) platform is the customized NTC-200 cell line, a proprietary cell line derived from normal human retinal pigment epithelial cells.  NTC-200 cells were initially screened from many other cell types as being remarkably hardy: the cells thrive under low oxygen and low nutrient conditions while being amenable to genetic manipulations under stringent selection methods.  The NTC-200 cell line can be genetically engineered to produce clinically relevant levels of therapeutic protein.

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The cell line can be custom designed for various indications.

ECT is a unique and versatile platform with the ability to continuously produce and deliver targeted therapeutics both singly or in combination, to the back of the eye long-term with no immunologic effect. Recombinant cell lines derived from transfected NTC-200 cells are able to secrete major classes of therapeutics, including antibodies, fusion proteins, and growth factors, potentially enabling the ECT platform to treat a broad array of chronic ocular diseases.

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The NTC-201-6A cell line produces human ciliary neurotrophic factor (CNTF), a protein that has been extensively studied as a neuroprotective factor.

Ciliary neurotrophic factor (CNTF), a neurotrophic factor naturally produced by neurons and Muller cells, has been extensively studied since its identification over three decades ago.  In several model systems of retinal disease, CNTF has been shown to have a neuroprotective effect on photoreceptors, the cells responsible for detecting light and retinal ganglion cells, the neuron that transmits vision to the brain.  Data suggest that CNTF slows vision loss by slowing or preventing neuron death.  As shown in the image below the eyes treated with CNTF have a higher number of photoreceptors remaining in the outer nuclear layer (ONL), while the non-treated diseased eyes progressively lost photoreceptors.

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“Tao et al., IOVS 2002 43:3292-3298”

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CNTF is hypothesized to function by binding to a tripartite receptor consisting of CNTFR, LIFR and GP130 which activates the JAK/STAT pathway and engages cell survival pathways in degenerating neurons.

Publications

CLINICAL

Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2. Ophthalmology. 2018.

Ciliary neurotrophic factor (CNTF) for human retinal degeneration: Phase I trial of CNTF delivered by encapsulated cell intraocular implants. Proc Natl Acad Sci USA 103 (10): 3896-901. 2006

Two-year intraocular delivery of ciliary neurotrophic factor by encapsulated cell technology implants in patients with chronic retinal degenerative diseases. Invest Ophthalmology Vis Sci. 53(12):7484-7491. 2012

Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic factor treatment. Invest Ophthalmol Vis Sci. 52(5):2219-26. 2011

Ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for treatment of geographic atrophy in age-related macular degeneration. Proc Natl Acad Sci USA. 108(15):6241-5. 2011

PRECLINICAL

CNTF induces dose-dependent alterations in retinal morphology in normal and rcd1 canine retina. Exp Eye Res. 2006 Mar;82(3):395-404.

CNTF and retina. Prog Retin Eye Res. (2):136-51. 2012

Encapsulated cell-based intraocular delivery of ciliary neurotrophic factor in normal rabbit: Dose-dependent effect on ERG and retinal histology. IOVS, Vol. 45 (7) 2420-2430. 2004.

Application of encapsulated cell technology for retinal degenerative diseases. Expert Opin Biol Ther. 6(7):717-26. 2006

Sustained secretion of ciliary neurotrophic factor to the vitreous, using the encapsulated cell therapy-based NT-501 intraocular device. Tissue Engineering, Vol. 10 (11/12):1617-1622. 2004.

Encapsulated cells as therapy. Scientific American 280:76. 1999                 

Encapsulated Cell-Based Delivery of CNTF Reduces Photoreceptor Degeneration in Animal Models of Retinitis Pigmentosa. IOVS, Vol. 43 (10) 3292-3298. 2002.

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