Treatment of Macular Degeneration Using Human Somatic Cell Nuclear Transfer Embryonic Stem cell Derived Retinal Pigment Epithelium: 1-Year Results in an Asian Patient

Abstract

Purpose : This study assessed safety and tolerability of the first clinical application of somatic cell nuclear transfer human embryonic stem cell(SCNT-hES)-derived cells for the treatment of macular degeneration in human.

Methods : We have established patient SCNT-hES from skin fibroblasts. Retinal pigment epithelium(RPE) have been derived from SCNT-hES at GMP facility. SCNT-hES-RPE met GMP standards consistent to the clinical grade hES-RPE. Korean ministry of food and drug safety authorized the clinical trial. Subretinal transplantation of SCNT-hES-RPE in an Asian female patient with advanced dry age related macular degeneration(AMD) was performed. No immunosuppressant was administered. The patient was closely monitored in terms of systemic and ophthalmologic safety for a year.

Results : Pigmentations were noted at subretinal and preretinal area without definite evidence of rejection, adverse proliferation and ectopic tissue formation. An epiretinal membrane(ERM) with dark brown pigmentation developed at postoperative 2 weeks. The ERM enlarged causing minimal thickening of the underlying retina, and the pre-retinal pigmentation area increased and darkened by 52 weeks. Best corrected visual acuity(BCVA) was 21 letters read on Bailey-Lovie chart at screening and stable through 24 weeks(22 letters read). BCVA was decreased to 10 letters read at 43 weeks and cataract with NO4 NC3 grade was also presented in the treated eye. At 52 weeks, the ERM was removed with standard 23 gauge 3 ports pars plana vitrectomy. The cataract was also extracted with phacoemulsification and the intraocular lens was implanted in the posterior chamber. After 2 weeks of the surgery, BCVA recovered to 21 letters read and the retinal thickening was remarkably decreased. No systemic and ophthalmologic serious adverse events related to transplanted cells were noted for 54 weeks.

Conclusions : These results confirmed the preliminary safety and tolerability of SCNT-hES-RPE therapy. Continued follow-up and further investigation in larger number of participants are necessary to determine the long-term safety and efficacy of SCNT-hES-derived cells as a potential source of replacement cells for the treatment of macular degeneration.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Baseline fundus photography with geographic atrophy

 

Fundus photography at postoperative 52 weeks reveals a subretinal and epiretinal pigmentations