title: Sustained secretion of ciliary neurotrophic factor to the vitreous, using the encapsulated cell therapy-based NT-501 intraocular device.
abstract: The objective of this study was to evaluate the in vivo secretion profile of ciliary neurotrophic factor (CNTF) from either of two genetically engineered cell lines contained in the encapsulated cell therapy (ECT)-based NT-501 device. ECT devices were loaded with either a low or high CNTF-secreting cell line and implanted into rabbit eyes for 1, 3, 7, 14, 30, 60, 90, 135, 180, or 365 days. After explantation, the vitreous was sampled and devices were allowed to incubate in endothelial serum-free medium for 24 h at 37 degrees C. Both the vitreous and the conditioned medium were assayed for CNTF using an ELISA. Device and vitreous CNTF, were plotted against time, and regression analysis was used to calculate half-life. Devices loaded with either cell line showed stable in vivo output for the duration of the study, with populations of healthy cells remaining in the device at study termination. For the low-dose CNTF-secreting cell line, with the final time point at 6 months, the halflife was estimated as 71 days, whereas the high-dose devices, with a final time point of 1 year, had an associated half-life of approximately 198 days. The NT-501 device is capable of delivering CNTF to the vitreous for at least 1 year. This ECT-based device, which has been shown to be safe and effective by our group, is a well-engineered ECT-based controlled delivery system capable of protein output on the order of years.
authors.affiliation: Neurotech USA, Lincoln, Rhode Island, USA. c.thanos@hotmail.com
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Thanos
authors.forename: William J
authors.initials: WJ
authors.lastname: Bell
authors.forename: P
authors.initials: P
authors.lastname: O'Rourke
authors.forename: Konrad
authors.initials: K
authors.lastname: Kauper
authors.forename: Sandy
authors.initials: S
authors.lastname: Sherman
authors.forename: Paul
authors.initials: P
authors.lastname: Stabila
authors.forename: Weng
authors.initials: W
authors.lastname: Tao
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002460:Cell Line; D020934:Ciliary Neurotrophic Factor / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D004343:Drug Implants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D008657:Metabolic Clearance Rate; D011817:Rabbits; D012160:Retina / Q000378:metabolism* / Q000637:transplantation*; D023822:Tissue Engineering / Q000379:methods; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism*
chemical_list: D020934:Ciliary Neurotrophic Factor; D004343:Drug Implants