Intracerebral Transplantation of Fetal Ventral Mesencephalon for Patients with Advanced Parkinson's Disease

Abstract

In order to launch a new transplantation program for Parkinson''s disease (PD), we evaluated the safety and efficacy of fetal ventral mesencephalic grafts in 3 patients with advanced PD. Inclusion criteria and clinical evaluation followed strictly the Core Assessment Program for Intracerebral Transplantation. The transplantation procedure was based on the technique previously described by the groups in Lund (Sweden) and Creteil (France). The putamen contralateral to the site of predominant symptoms was unilaterally grafted in all patients. Magnetic resonance (MR)-based stereotactic guidance with multiplanar correlation was used to define 3 implantation trajectories in the precommissural, commissural, and postcommissural putamen. Fetal ventral mesencephalon was prepared from 6- to 8-week-old human embryos obtained from same-day abortions. Under general anesthesia, 8 deposits of 3 µl of the fetal tissue were placed 1 mm apart along each implantation trajectory using a customized microsyringe and needle attached to the stereotactic frame. The patients recovered uneventfully from the neurosurgical procedure. Early postoperative MR clearly showed the implantation trajectories reaching the putamen in all patients. The follow-up period was of 12, 9 and 6 months, for each of the 3 patients, respectively. Clinical changes appeared between 3 and 6 months after transplantation and consisted of an increase in the ‘on’ periods and in quantitative bilateral improvement in the motor timed tests. There was an improvement of the Unified Parkinson''s Disease Rating Scale score and an improvement of rigidity. Tremor was unchanged, and there was a slight and transient increase in dyskinesias. Neuropsychological follow-up revealed slight frontal alterations in 2 patients. Positron emission tomography demonstrated an increase of ¹⁸F-fluorodopa uptake in the grafted site. Adverse events include a reversible Cushing syndrome secondary to immunosuppression in 1 patient and a transient episode of confusion in another. The results of this study, designed as a prerequisite for a wider transplantation program, are in accordance with those previously reported by others and show that, using standardized neurosurgical techniques and methods of evaluation, transplantation is a reproducible and safe therapeutic approach which provides clinical benefits to patients with advanced PD.

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).…”

Imaging in cell-based therapy for neurodegenerative diseases

“…Graft viability has also been shown using PET [36,41,42,[104][105][106]. Importantly, the recovery of dopamine function being was found to be dependant on the amount of fetal tissue implanted [107].…”

The serotonergic system in Parkinson’s patients with dyskinesia: evidence from imaging studies

“…This treatment showed robust efficacy in some patients with remarkable improvement of motor symptoms but was also associated to severe adverse reactions consisting of developing troublesome involuntary movements when ‘off’ their dopaminergic drugs, called GIDs (Freed et al 1990, 1992; Hagell et al 2002; Levivier et al 1997; Lindvall et al 1990, 1992; Ma et al 2002; Olanow et al 2009; Peschanski et al 1994; Widner et al 1992). Graft tissue contained a varied proportion of non-dopaminergic cells including serotonergic neurons.…”