Implantation of Human Fetal Ventral Mesencephalon to the Right Caudate Nucleus in Advanced Parkinson's Disease

Henderson, Bruce T. H.; Clough, Chris; Hughes, R. C.; Hitchcock, Edward; Kenny, Brendan

doi:10.1001/archneur.1991.00530200062020

Cited by 140 publications

(36 citation statements)

References 51 publications

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“…[71][72][73][74][75][76][77][78][79] For human fetal mesencephalon transplantation, 19 papers were found and all were included. 13,75,[80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96] Once the evidence regarding all the articles reviewed was classified, each working group summarized all the collected data and indicated the quality of evidence of all citations contributing to their recommendations. A draft of this document was circulated among all the study participants for their final review and comments.…”

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confidence: 99%

Evaluation of surgery for Parkinson’s disease

Hallett¹,

Litvan²

1999

Neurology

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the Task Force on Surgery for Parkinson's Disease* PD is a common disorder affecting on average 100 per 100,000 population. Despite the large number of medications available for the treatment of early and moderately advanced PD, options specifically designed for the patient with advanced disease are limited. Surgery for PD dates from 1939-1940, when Bucy and Case 1 and Klemme 2 excised parts of the cerebral cortex to treat tremor and dystonia, but this type of surgery produced hemiparesis. Surgical basal ganglia lesions were introduced a few years later by Meyers, 3,4 who found that pallidotomy produced significant relief of tremor, rigidity, and dyskinesias, but with considerable mortality. Stereotaxic techniques to coagulate the globus pallidus in PD were introduced in the 1950s by Spiegel and Wycis, 5,6 and Cooper was an early advocate of pallidal surgery.7 Based on the anatomic connections between the pallidum and the thalamus, Hassler introduced the concept of surgery on the ventrolateral nucleus of the thalamus. 8,9Microelectrode recording allowed Narabayashi 10,11 to find that lesioning the ventral intermediate (Vim) nucleus of the thalamus was the most specific target to control the tremor in PD. Neurosurgery reached its peak in the 1960s, but declined after the introduction of levodopa.The recent resurgence of surgery was initiated by adrenal medullary transplantation. The premise of adrenal medullary transplants was that these cells, when transplanted into patients with advanced PD, would survive and function as a new source of dopamine. The theoretical advantages of adrenal tissue include that the tissue comes from the patient, eliminating the issue of immunologic rejection; dopamine is a normal intermediate compound made by the chromaffin cells; and chromaffin cells may have neuritic morphology when grown in culture. The disadvantages include the non-neuronal source and the rather modest survival rates of cells in laboratory transplantation studies. Isolated case reports of effective treatment of advanced PD with unilateral transplantation of adrenal medullary cells into the striatum in the 1980s led to several clinical trials testing the safety and efficacy of this procedure.Fetal mesencephalon transplantation was introduced subsequently and is based on several considerations. First, PD is associated with relatively selective degeneration of dopaminergic cells located in the substantia nigra, a portion of the mesencephalon. Second, replacement of dopaminergic activity by means of precursor drugs, receptor agonists, or inhibitors of dopamine catabolism improves the signs and symptoms of PD. Third, laboratory evidence in experimental animals has demonstrated that grafts of dopamine-containing neurons improve behavioral models of PD. Fourth, in these animal models, grafts reinnervate the striatum and form synaptic connections with host neurons. As a result, a small number of research teams have developed programs for human fetal mesencephalic cell grafts in PD patients. Several published reports exist,...

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confidence: 99%

Evaluation of surgery for Parkinson’s disease

Hallett¹,

Litvan²

1999

Neurology

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“…At least six groups have reported improvement in motor fluctuations after fetal tissue implantation in open-label studies. 1,[5][6][7][8]11 There is no way to know, however, whether improvements reported by those groups was due to placebo effect. Only additional placebo-controlled studies can settle this question.…”

Section: Why Was No Improvement Seen In Medication-related Motor Flucmentioning

confidence: 99%

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

Greene¹,

Fahn²

2002

FOC

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In the first double-blind, placebo-controlled randomized study of fetal tissue transplantation for the treatment of patients with advanced Parkinson disease (PD), investigators found that implanted dopaminergic tissue can produce measurable improvement in young PD in the absence of medication (that is, the “off” state). The results of the study, however, also highlighted several serious limitations of transplantation. In the group of older patients in the study (in the typical age range of individuals afflicted with PD) no improvement was derived from the implant despite positron emission tomography–documented scan evidence that the graft survived and produced dopamine. Patients in the study were selected because they experienced motor fluctuations, and the transplant did not improve dyskinesias or the time required to remain “on” medication for any subgroup of patients, including young patients. Five of 33 implant-treated patients developed involuntary movements (dyskinesias or dystonia) that could not be eliminated by reducing antiparkinsonian medications. These included four patients with the best responses to transplantation. Finally, some sham-operated patients experienced a dramatic placebo effect lasting at least 1 year, which justified the controversial sham surgery. The authors believe that these problems must be solved before fetal tissue transplantation can be considered a therapeutic option for PD.

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“…To date, in human trials material from between one and eight fetuses per patient has been used. [15,26,29,34,35,37,41,46,[49][50][51]53,55,56,60,61,69,71,73,77] The use of fetal tissue does have two significant drawbacks, however. One is purely logistical.…”

Section: Strategies For Transplantation In Parkinson's Diseasementioning

confidence: 99%

“…The issues of primacy notwithstanding, several groups around the world were poised to use fetal tissue in human trials at that time, and over the next 1 to 2 years, implantation of fetal tissue was performed at additional centers in Cuba, the United Kingdom, and the United States. [26,27,35,60,61] Numerous other centers throughout the world embarked on similar studies in the 1990s. [15,19,30,34,37,41,48,53,69,71,74] By the mid 1990s, a body of evidence had accrued to suggest that fetal cell implants were superior to adrenal medullary implants and could, in fact, produce lasting clinical effects in patients with PD.…”

Section: Clinical Trials In Parkinson's Diseasementioning

confidence: 99%

An overview of central nervous system transplantation in human disease

Breeze¹,

Wang²

1999

FOC

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Although its roots date back over a century, the field of neurotransplantation has been shaped mostly by advances over the past 30 years. Animal models of nigrostriatal disconnection in the 1970s allowed investigators to explore the feasibility of neural grafting. By the end of that decade, functional and behavioral effects had been demonstrated using fetal tissue grafts. In the 1980s, animal experimentation continued, as did clinical trials involving patients with idiopathic Parkinson's disease. Both autologous adrenal medullary tissue and fetal allografts were tested in the clinical setting, with the latter proving to yield superior results. Animal models of striatal cell loss provided the impetus for limited clinical trials in patients with Huntington's disease by the early 1990s, and work with both diseases continues today. Although much has been learned, neural grafting remains experimental. Broader applications are being explored even now, though, as transplant techniques are applied to animal models of dementia, spinal cord injury, cortical injury, and pain. Some very limited human trials have already begun in some of these areas. In this review some of the advances in the field are highlighted.

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Implantation of Human Fetal Ventral Mesencephalon to the Right Caudate Nucleus in Advanced Parkinson's Disease

Cited by 140 publications

References 51 publications

Evaluation of surgery for Parkinson’s disease

Evaluation of surgery for Parkinson’s disease

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

An overview of central nervous system transplantation in human disease

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