Intrastriatal Implantation of Human Retinal Pigment Epithelial Cells Attached to Microcarriers in Advanced Parkinson Disease

Abstract

Background: Human retinal pigment epithelial (RPE) cells produce levodopa and can be isolated from postmortem human eye tissue, grown in culture, and implanted into the brain attached to microcarriers. These implants ameliorated the motor deficits in rodent and nonhuman primate models of Parkinson disease. Objective: To evaluate the safety and efficacy of unilateral implantation of human RPE cells attached to gelatin microcarriers into the putamen contralateral to the more symptomatic side of patients with Parkinson disease.

Modulation of Abnormal Metabolic Brain Networks by Experimental Therapies in a Nonhuman Primate Model of Parkinson Disease: An Application to Human Retinal Pigment Epithelial Cell Implantation

“…The parkinsonian animals were evaluated before and 6-48 mo after unilateral striatal implantation (Fig. 1A) and rated as mild moderate (n 5 7) or moderately severe (n 5 1) at the time of imaging (motor score, 11.9 6 5.1; range, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23].…”

“…Human retinal pigment epithelial (hRPE) cells of fetal origin, attached to gelatin microcarriers (GM; hrPE-GM) for enhanced survival, have been used as a potential therapy to reverse parkinsonian motor deficits in rodents (11,12), in monkeys (13,14), and, under the name Spheramine (Titan Pharmaceuticals, Inc.), in PD patients (15,16). There is unequivocal evidence that hRPE-GM implants can survive without immunosuppression (17,18) as in fetal cell transplantation in PD patients (19).…”

Dopamine Cell Transplantation for Parkinson's Disease: The Importance of Controlled Clinical Trials

“…A similar outcome was seen with a manufactured product, Spheramine (Mfg: Titan Pharmaceuticals, South San Francisco, CA), which combined human retinal pigment epithelial cells with a microcarrier support matrix, which was then injected into the putamen. Although results of a phase I open clinical trial were positive [15], the double-blind phase II trial failed to show any benefit.…”

High efficiency non-viral transfection of retinal and iris pigment epithelial cells with pigment epithelium-derived factor

“…[1][2][3][4][5][6][7][8][9] Since in vivo an equilibrium of neurotrophic factors, such as pigment epithelium-derived factor (PEDF), fibroblast growth factor, platelet-derived growth factor and others, supports the survival of neural tissues, it may be necessary to transplant cells that have been genetically modified to express these factors to achieve optimal functional improvement. In fact, in vitro and in vivo studies have shown that supplementation with various growth factors prevents or delays photoreceptor degeneration and increases the function of dopaminergic tissue in animal models of retinal degeneration and PD.…”