Therapeutic Potentials of Human Embryonic Stem Cells in Parkinson’s Disease

Newman, Mary B.; Bakay, Roy A.E.

doi:10.1016/j.nurt.2008.02.004

Cited by 31 publications

(17 citation statements)

References 137 publications

(114 reference statements)

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“…Derivation of dopamine neurons from hESCs has been one of the primary cell types pursed as a target for developing stem cell therapies to treat Parkinson's disease [30] . Parkinson's disease is a neurodegenerative disorder that involves specific degeneration of dopamine neurons within the substantia nigra regions of the brain.…”

Section: Dopamine Neuronsmentioning

confidence: 99%

Signals Involved in Neural Differentiation of Human Embryonic Stem Cells

Denham

Dottori²

2009

Neurosignals

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Neural differentiation from embryonic stem cells involves progressive stages of neural induction, expansion and maintenance of neural stem/progenitor cells, and differentiation to neurons and glia. Our understanding of the signals involved in each of these processes is primarily based on our knowledge of neural development during embryogenesis. This review will focus on the signalling pathways that have been identified to play a role in neural differentiation of human embryonic stem cells (hESCs), including their induction to neuroectoderm, maintenance and expansion of hESC-derived neurospheres, differentiation to neurons and specification to specific neuronal lineages. Understanding the signals involved in each of these stages is important for optimising methods to derive specific cell types for transplantation therapies, as well as for providing insight into the mechanisms of human neurogenesis.

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Section: Dopamine Neuronsmentioning

confidence: 99%

Signals Involved in Neural Differentiation of Human Embryonic Stem Cells

Denham

Dottori²

2009

Neurosignals

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“…A number of benefits have been reported for cell transplantation in models of clinically intractable diseases such as Parkinson's disease, 7 Huntington's disease, 8 and temporal lobe epilepsy. 9 These data demonstrate that this approach may have the potential to serve as a surgical alternative for pharmacoresistant neurological diseases associated with lost or damaged brain tissue.…”

Section: Cell-based Therapy For Neurological Diseasesmentioning

confidence: 99%

Transplantation of GABA-Producing Cells for Seizure Control in Models of Temporal Lobe Epilepsy

Thompson

2009

Neurotherapeutics

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Summary:A high percentage of patients with temporal lobe epilepsy (TLE) are refractory to conventional pharmacotherapy. The progressive neurodegenerative processes associated with a lifetime of uncontrolled seizures mandate the development of alternative approaches to treat this disease. Transplantation of inhibitory cells has been suggested as a potential therapeutic strategy to achieve seizure suppression in humans with intractable TLE. Preclinical investigations over 20 years have demonstrated that multiple cell types from several sources can produce anticonvulsant, and antiepileptogenic, effects in animal models of TLE. Transplanting GABA-producing cells, in particular, has been shown to reduce seizures in several well-established models. This review addresses experimentation using different sources of transplantable GABAergic cells, highlighting progress with fetal tissue, neural cell lines, and stem cells. Regardless of the source of the GABAergic cells used in seizure studies, common challenges have emerged. Several variables influence the anticonvulsant potential of GABA-producing cells. For example, tissue availability, graft survival, immunogenicity, tumorigenicity, and varying levels of cell migration, differentiation, and integration into functional circuits and the microenvironment provided by sclerotic tissue all contribute to the efficacy of transplanted cells. The challenge of understanding how all of these variables work in concert, in a disease process that has no well-established etiology, suggests that there is still much basic research to be done before rational cell-based therapies can be developed for TLE.

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“…Understanding this cascade of events provides several targets for therapy. These include correction of the original genetic defect via gene therapy, 20 reversal of the basic biochemical defects for symptomatic benefit or neuroprotection, 21 replacement of depleted dopamine stores or dopamine neurons, 22 or interruption of abnormal basal ganglia output via deep brain stimulation. 23,24 As another example, dopa-responsive dystonia may begin with a mutation in the GCH1 gene (FIG.…”

Section: Rational Design: Prototype Disorder Strategymentioning

confidence: 99%

Experimental Therapeutics for Dystonia

Jinnah

Hess

2008

Neurotherapeutics

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Summary: Dystonia is a neurological syndrome characterized by excessive involuntary muscle contractions leading to twisting movements and unnatural postures. It has many different clinical manifestations, and many different causes. More than 3 million people worldwide suffer from dystonia, yet there are few broadly effective treatments. In the past decade, progress in research has advanced our understanding of the pathogenesis of dystonia to a point where drug discovery efforts are now feasible. Several strategies can be used to develop novel therapeutics for dystonia. Existing therapies have only modest efficacy, but may be refined and improved to increase benefits while reducing side effects. Identifying rational targets for drug intervention based on the pathogenesis of dystonia is another strategy. The surge in both basic and clinical research discoveries has provided insights at all levels, including etiological, physiological and nosological, to enable such a targeted approach. The empirical approach to drug discovery, whereby compounds are identified using a nonmechanistic strategy, is complementary to the rational approach. With the recent development of multiple animal models of dystonia, it is now possible to develop assays and perform drug screens on vast numbers of compounds. This multifaceted approach to drug discovery in dystonia will likely provide lead compounds that can then be translated for clinical use.

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Therapeutic Potentials of Human Embryonic Stem Cells in Parkinson’s Disease

Cited by 31 publications

References 137 publications

Signals Involved in Neural Differentiation of Human Embryonic Stem Cells

Signals Involved in Neural Differentiation of Human Embryonic Stem Cells

Transplantation of GABA-Producing Cells for Seizure Control in Models of Temporal Lobe Epilepsy

Experimental Therapeutics for Dystonia

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