Neurotransplantation in Parkinson's Disease: From Open Microsurgery to Bilateral Stereotactic Approach: First Clinical Trial Using Microelectrode Recording Technique

Abstract

This paper summarizes the results of three controlled clinical trials related to the transplantation of embryonic ventral mesencephalic tissue into the striatum of 46 idiopathic parkinsonian patients exhibiting motor complications on standard levodopa therapy. From January 1988 to April 1990, 30 subjects with fluctuating Parkinson''s disease received fetal dopaminergic tissue implants by the open microsurgical technique. In March 1992 the stereotactic approach was adopted for successive fetal mesencephalic cell suspension transplants (7 unilateral and 9 bilateral) into the caudate and putamen of parkinsonian patients with levodopa-induced complex fluctuations and dyskinesias. The neurological assessment performed 12 months before and 3–18 months after transplantation demonstrated a reduction of both the daily time spent in the ''off condition and the number of daily ''off periods, and a significant improvement of the motor scale. The stereotactic selective thalamotomy with microelestrode recording was introduced in January 1993, in order to provide a further potential treatment strategy; i.e., the combination of the two surgical trends in Parkinson''s disease, the restorative neurotransplantation technique, and the selective lesional approach. In addition to that, microelectrode recording is also used for implantation site selection and functional characterization.

Influence of cell preparation and target location on the behavioral recovery after striatal transplantation of fetal dopaminergic neurons in a primate model of Parkinson’s disease

“…(Freed et al, 1992;Freed et al, 2001;Freeman et al, 1995;Hagell et al, 1999;Levivier et al, 1997;Lindvall et al, 1990;Lindvall et al, 1992;Lopez-Lozano et al, 1997b;Mendez et al, 2002;Mendez et al, 2005;Molina et al, 1994;Olanow et al, 2003;Peschanski et al, 1994;Piccini et al, 1999;Piccini et al, 2000;Spencer et al, 1992). In many cases patients showed significant clinical improvements and in several cases, they were able to eliminate their dopamine medication altogether (Lindvall et al, 1994).…”

L‐DOPA for Parkinson's disease—a bittersweet pill

“…After much practical refinement of the approaches, both reached open label clinical trials in the late 1980s (Backlund et al., ; Goetz et al., ; Kelly et al., ). Although ethically compromised, the most clinically successful approach was the use of early stage foetal ventral mesencephalic cells to the extent that several small open label studies and two US government funded double‐blind trials were delivered (Freed et al., ; Hagell & Brundin, ; Kopyov, Jacques, Lieberman, Duma, & Rogers, , ; Levivier et al., ; Lindvall et al., ; Molina et al., ; Olanow et al., ; Spencer et al., ).…”

Fetal stem cell transplantation: Past, present, and future

“…Such clinical results have encouraged many researchers worldwide to apply this therapeutic approach as a treatment for PD. Namely, fetal brain tissue transplantation, which began in China [2,80] , has been attempted in Canada [81] , Cuba [82] , the Czech Republic [83] , France [84] , Mexico [1] , Poland [85] , Slovakia [86] , Spain [87,88] , United Kingdom [71,89] , United States [2,3,73,77,90,91] , and USSR (currently Russia) [92] . Moreover, the Network of European CNS Transplantation and Restoration (NECTAR) was founded in 1990 to bring together European groups who share the common goal of protecting, repairing and restoring the central nervous system damage resulting from degenerative diseases and/or injury [93] .…”