Status of fetal tissue transplantation for the treatment of advanced Parkinson disease

Greene, Paul; Fahn, Stanley

doi:10.3171/foc.2002.13.5.4

Cited by 15 publications

(6 citation statements)

References 8 publications

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“…(3) Last, both the clinical amelioration and the SEP amplitude increase induced by the electrode implant before the start of stimulation might be related to the expectation of motor improvement. Recently, there have been several instances of evidence of a placebo effect in parkinsonian patients 9, 13, 15. Placebo may induce release of dopamine in the dorsal striatum,11, 12 and may have an apomorphine‐like effect on motor symptoms and SEP amplitude.…”

Section: Discussionmentioning

confidence: 99%

Somatosensory evoked potential and clinical changes after electrode implant in basal ganglia of parkinsonian patients

Insola¹,

Mazzone²,

Valeriani

2005

Muscle and Nerve

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Median nerve somatosensory evoked potentials (SEPs) were recorded in three parkinsonian patients who underwent electrode implant in the subthalamic nucleus and/or globus pallidus for chronic deep brain stimulation (DBS). SEPs were evoked before surgery, in a medication-free condition, and after the functional stereotactic procedure, before beginning DBS. In order to evaluate the timing of the SEP changes after the electrode implant, in three further patients SEPs were recorded within the operating theater, before and immediately after the implantation. Patients' symptoms improved immediately after the electrode implant, and both N20 and N30 amplitudes increased in the postsurgical SEP recording. The clinical and neurophysiological effects observed after surgery, before commencing DBS, can be explained by microdamage in the target nucleus following the electrode implant. They occurred also in the patients studied in the operating theater, thus suggesting that they occur immediately after the stereotactic procedure. Our results suggest that the circuitries between the basal ganglia and the primary sensorimotor cortex may be modified not only by DBS but also by microdamage due to surgery and that they exert an important influence on SEP amplitude.

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Section: Discussionmentioning

confidence: 99%

Somatosensory evoked potential and clinical changes after electrode implant in basal ganglia of parkinsonian patients

Insola¹,

Mazzone²,

Valeriani

2005

Muscle and Nerve

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“…Although these clinical trials clearly indicate room for improvement to enhance graft function as well as reduce unwarranted dyskinetic side effects, they also indicate positive short‐term clinical benefit in a subset of patients similar to open‐label trials and highlight potential problems to tackle, understand, and eventually resolve in future studies (reviews150–154). Specifically, a consensus must come to a standardization for method of dissection, age and number of donor fetuses, length of tissue incubation postisolation, as well as the target site, number of sites to graft, and a variety of other surgical parameters with clinical relevance reviewed elsewhere 45,155.…”

Section: Neuronal Transplantation In Parkinson's Diseasementioning

confidence: 99%

Cell Transplantation and Gene Therapy in Parkinson's Disease

Wakeman

Dodiya

Kordower

2011

Mount Sinai J Medicine

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Parkinson's disease is a progressive neurodegenerative disorder affecting, in part, dopaminergic motor neurons of the ventral midbrain and their terminal projections that course to the striatum. Symptomatic strategies focused on dopamine replacement have proven effective at remediating some motor symptoms during the course of disease but ultimately fail to deliver long-term disease modification and lose effectiveness due to the emergence of side effects. Several strategies have been experimentally tested as alternatives for Parkinson's disease, including direct cell replacement and gene transfer through viral vectors. Cellular transplantation of dopamine-secreting cells was hypothesized as a substitute for pharmacotherapy to directly provide dopamine, whereas gene therapy has primarily focused on restoration of dopamine synthesis or neuroprotection and restoration of spared host dopaminergic circuitry through trophic factors as a means to enhance sustained controlled dopamine transmission. This seems now to have been verified in numerous studies in rodents and nonhuman primates, which have shown that grafts of fetal dopamine neurons or gene transfer through viral vector delivery can lead to improvements in biochemical and behavioral indices of dopamine deficiency. However, in clinical studies, the improvements in parkinsonism have been rather modest and variable and have been plagued by graft-induced dyskinesias. New developments in stem-cell transplantation and induced patient-derived cells have opened the doors for the advancement of cell-based therapeutics. In addition, viral-vector-derived therapies have been developed preclinically with excellent safety and efficacy profiles, showing promise in clinical trials thus far. Further progress and optimization of these therapies will be necessary to ensure safety and efficacy before widespread clinical use is deemed appropriate.

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“…The most successful clinical example for using progenitor cell or embryonic tissue to combat neurodegenerative disease is the implantation of embryonic fetal mesencephalic tissue into a cavity of Parkinson's disease patient’s caudate nucleus. Results of these trials indicate different magnitudes of benefit that remained apparent at 5 -10 years following cell implants [78-82]. …”

Section: Therapeutic Potential Of Apα Has a Re-generative Factormentioning

confidence: 99%

Regeneration in a Degenerating Brain: Potential of Allopregnanolone as a Neuroregenerative Agent

Wang¹,

Irwin²,

Liu³

et al. 2007

CAR

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Confronting the efficacy of a regenerative therapeutic is the degenerative environment that is characterized by neuronal loss, physical plague and glial scar barriers and inflammation. But perhaps more fundamental from a regenerative perspective, are changes in the biochemical milieu of steroid and peptide growth factors, cytokines and neurotransmitter systems. Data from multiple levels of analysis indicate that gonadal steroid hormones and their metabolites can promote neural health whereas their decline or absence are associated with decline in neural health and increased risk of neurodegenerative disease including Alzheimer’s. Among the steroids in decline, is allopregnanolone (APα), a neurosteroid metabolite of progesterone, which was found to be reduced in the serum [1,2] and plasma [3] and brain of aged vs. young subjects [4]. Further, Alzheimer disease (AD) victims showed an even further reduction in plasma and brain levels of APα relative to age-matched neurologically normal controls [1,4,5]. Our earlier work has shown that APα is a neurogenic agent for rodent hippocampal neural progenitors and for human neural progenitor cells derived from the cerebral cortex [6]. Our ongoing research seeks to determine the neurogenic potential of APα in the triple transgenic mouse model of Alzheimer’s disease (3xTgAD) as AD related pathology progresses from imperceptible to mild to severe. Initial analyses suggest that neurogenic potential changes with age in nontransgenic mice and that the neurogenic profile differs between non-transgenic and 3xTgAD mice. Comparative analyses indicate that APα modifies neurogenesis in both non-transgenic and 3xTgAD mice. Preliminary data suggest that APα may modify Alzheimer’s pathology progression. Together the data indicate that APα may maintain the regenerative ability of the brain and modify progression of AD related pathology. Challenges for efficacy of regenerative agents within a degenerative milieu are discussed.

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Status of fetal tissue transplantation for the treatment of advanced Parkinson disease

Cited by 15 publications

References 8 publications

Somatosensory evoked potential and clinical changes after electrode implant in basal ganglia of parkinsonian patients

Somatosensory evoked potential and clinical changes after electrode implant in basal ganglia of parkinsonian patients

Cell Transplantation and Gene Therapy in Parkinson's Disease

Regeneration in a Degenerating Brain: Potential of Allopregnanolone as a Neuroregenerative Agent

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