Intrastriatal implantation of human retinal pigment epithelial cells attached to microcarriers in advanced Parkinson disease.
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.


METHODS
Open-label pilot study.


METHODS
A tertiary referral center for movement disorders.


METHODS
Six patients with advanced Parkinson disease.


METHODS
We performed stereotactic intrastriatal implantation of approximately 325,000 RPE cells on microcarriers.


METHODS
Change from baseline to 12 months in the Unified Parkinson's Disease Rating Scale motor subscore with the patients in the practically defined off state (not taking antiparkinsonian medications for at least 12 hours overnight).


RESULTS
The implants were well tolerated. We observed an average improvement of 48% at 12 months after implantation in the Unified Parkinson's Disease Rating Scale motor subscore with the patient in the off state, which was sustained through 24 months. Improvement was also observed in activities of daily living, quality of life, and motor fluctuations. No off-state dyskinesias were observed.


CONCLUSIONS
Implants of human RPE cells attached to gelatin microcarriers appear to be safe and well tolerated, and they improved motor symptoms in patients with Parkinson disease. On the basis of these results, a randomized, double-blind, placebo-controlled study has been initiated.
Stover
Natividad P
NP
Department of Neurology, University of Alabama at Birmingham, 35233-0017, USA. npstover@uab.edu
Bakay
Roy A E
RA
Subramanian
Thyagarajan
T
Raiser
Cathy D
CD
Cornfeldt
Michael L
ML
Schweikert
Alfred W
AW
Allen
Richard C
RC
Watts
Ray L
RL
D000978:Antiparkinson Agents / Q000627:therapeutic use; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000503:physiopathology; D003342:Corpus Striatum / Q000503:physiopathology / Q000601:surgery*; D003866:Depressive Disorder / Q000209:etiology / Q000503:physiopathology; D005780:Gelatin / Q000627:therapeutic use; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007980:Levodopa / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D010300:Parkinson Disease / Q000601:surgery*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D010865:Pilot Projects; D011183:Postoperative Complications / Q000209:etiology / Q000503:physiopathology; D011699:Putamen / Q000503:physiopathology / Q000601:surgery; D020127:Recovery of Function / Q000502:physiology; D013238:Stereotaxic Techniques; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D007980:Levodopa; D005780:Gelatin