TY - CHAP

T1 - Strategies for bringing stem cell-derived dopamine neurons to the clinic

T2 - A European approach (STEM-PD)

AU - Kirkeby, Agnete

AU - Parmar, Malin

AU - Barker, Roger A.

N1 - M1 - Copyright (C) 2018 U.S. National Library of Medicine. MEDLINE AN 2018620541(Journal; Article; (JOURNAL ARTICLE))

PY - 2017

Y1 - 2017

N2 - The treatment of Parkinson's disease (PD) has for over 50 years relied on dopaminergic therapies that are highly effective especially in the early years of the condition, but ultimately are limited by the development of side effects that relate to the nonphysiological stimulation of dopamine receptors including in nonstriatal areas. Targeted regenerative therapies designed to restore specifically the lost dopaminergic innervation of the striatum would therefore represent a major advance in treating PD. Transplantation of human fetal ventral midbrain tissue to the striatum of PD patients has provided proof-of-principle that such an approach can provide long-term clinical benefits with a reduced dependency on any oral dopaminergic agents. However, fetal tissue is associated with several ethical and logistical problems and therefore does not represent a realistic route to the clinical treatment of PD in the future. As a result, alternative cell sources have been explored and the methods for producing authentic midbrain dopaminergic neurons from pluripotent cells have now advanced to a stage which makes it possible to efficiently and reproducibly produce DA progenitors at a much higher purity than can be obtained from human fetal tissue. A stem cell-based therapy for PD therefore has the potential to circumvent many of the problems currently associated with fetal tissue grafting. Here, we describe the challenges faced and the strategies that have been pursued in our European effort to bring a human embryonic stem cell (hESC)-derived dopamine cell product to clinical trial for PD.[on SciFinder (R)]

AB - The treatment of Parkinson's disease (PD) has for over 50 years relied on dopaminergic therapies that are highly effective especially in the early years of the condition, but ultimately are limited by the development of side effects that relate to the nonphysiological stimulation of dopamine receptors including in nonstriatal areas. Targeted regenerative therapies designed to restore specifically the lost dopaminergic innervation of the striatum would therefore represent a major advance in treating PD. Transplantation of human fetal ventral midbrain tissue to the striatum of PD patients has provided proof-of-principle that such an approach can provide long-term clinical benefits with a reduced dependency on any oral dopaminergic agents. However, fetal tissue is associated with several ethical and logistical problems and therefore does not represent a realistic route to the clinical treatment of PD in the future. As a result, alternative cell sources have been explored and the methods for producing authentic midbrain dopaminergic neurons from pluripotent cells have now advanced to a stage which makes it possible to efficiently and reproducibly produce DA progenitors at a much higher purity than can be obtained from human fetal tissue. A stem cell-based therapy for PD therefore has the potential to circumvent many of the problems currently associated with fetal tissue grafting. Here, we describe the challenges faced and the strategies that have been pursued in our European effort to bring a human embryonic stem cell (hESC)-derived dopamine cell product to clinical trial for PD.[on SciFinder (R)]

KW - clinical trial

KW - dopaminergic neurons

KW - fetal ventral mesencephalic tissue

KW - good manufacturing practice (gmp)

KW - human embryonic stem cells

KW - parkinson's disease

KW - transeuro

KW - ventral midbrain

U2 - 10.1016/bs.pbr.2016.11.011

DO - 10.1016/bs.pbr.2016.11.011

M3 - Book chapter

C2 - 28552228

VL - 230

T3 - Progress in Brain Research

SP - 165

EP - 190

BT - Functional Neural Transplantation IV

ER -