Grafting of perfused adrenal medullary tissue into the caudate nucleus of patients with Parkinson's disease

Abstract

The authors report results obtained in 20 severely affected patients with Parkinson's disease (Grade IV or V) who received an autotransplant of perfused adrenal medullary tissue. This study seems to indicate that these autoimplants can improve the parkinsonian symptomatology and induce amelioration in the patients' performance of routine activities. All the symptoms analyzed showed improvement, although it differed in intensity and time of onset. Moreover, this improvement was accompanied by a reduction in the daily intake of L-dopa, with discontinuance of dopamine agonists and amantadine. A number of medical complications were encountered, including three deaths, probably related to performing abdominal surgery in seriously affected parkinsonian patients who were unable to tolerate the discontinuance of their medication. The transient psychiatric disorders observed appeared to be related to the postoperative dose of L-dopa and/or anticholinergic agents administered, and diminished or disappeared when the doses were reduced. The reasons for improvement, which was bilateral, remain unknown, although one cause may be the surgical trauma (minicaudotomy) together with the implantation of adrenal medullary tissue, which may promote the sprouting of surviving dopaminergic fibers. Moreover, in this series, perfusion of adrenal medulla increased the capacity for revascularization of the tissue and may have reduced the damaging effects of warm ischemia on the cells. This, together with the existence of fenestrated vessels, could hypothetically have served as an access point for drugs, and if the implanted cells were viable, they might have served to store and manufacture different factors and/or transmitters. These results as well as those of other groups justify the development of a controlled international clinical trial.

Evaluation of surgery for Parkinson’s disease

“…62,[66][67][68][69][70] There were 52 articles for adrenal medullary transplantation, but the review includes only the 9 that met criteria. [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.…”

“…Three ideas for modified protocols have evolved from these studies: first, special perfusion techniques aimed at increasing cell survival 75 ; second, the addition of trophic factors or peripheral nerve cotransplants to enhance cell survival; and third, the grafting of fetal adrenal medullary cells. Cotransplantation procedures combining adrenal medullary tissue with peripheral nerve fragments have been performed in two small series (<5 subjects each), and in each, selected patients improved.…”

“…Cotransplantation procedures combining adrenal medullary tissue with peripheral nerve fragments have been performed in two small series (<5 subjects each), and in each, selected patients improved. 75,107 The primary problem with adrenal surgery was the double procedure, abdominal and cerebral, involving two teams, long intraoperative time, and long recovery. 72 Morbidity was less with retroperitoneal surgery than frontalabdominal and less with stereotaxic than open craniotomy.…”

Promoter-activated expression of nerve growth factor for treatment of neurodegenerative diseases

“…[8][9][10] Fetal cholinergic implants have also reversed cognitive deficits of maze learning in rats with lesions of the fimbria-fornix, in an animal model of Alzheimer's disease. 11,12 In addition, adrenal tissue has been used as an alternative source of dopamine producing cells, 13,14 but does not appear to ameliorate deficits observed in animal models of Parkinson's disease. 15,16 More recent efforts have focused on the development of cultured or genetically modified cells that can serve as replacement cells for degenerating neurons in neurodegenerative disorders, or the use of cells capable of releasing specific trophic factors in brain-damaged regions.…”

Clinical neurotransplantation protocol for Huntington's and Parkinson's disease

“…In case of PD patients, they were grafted mainly into the putamen bilaterally, using between three to five donors per hemisphere (Lindvall 1992, Freed 1992. There were also reported cases of caudate nucleus transplantation (Henderson 1991, Molina 1991, Lopez-Lozano 1991, Spencer 1992 and of putamen and substantia nigra (SN) simultaneous transplantation (Mendez 2002). Several open-label trials reported clinical benefit and long-term graft sur-vival.…”