Preliminary Clinical Experience with Neural Transplantation: Two Case Reports

Summary

Parkinson’s disease is a chronic degenerative neurological disorder with progressive loss of nigrostriatal dopaminergic neurons and subsequent striatal dopamine deficiency. The treatment of choice is levodopa or dopamine-agonist replacement. However, long-term therapy is associated with severe side effects such as motor fluctuations and abnormal involuntary movements. Clinical trials with transplantation of human embryonic mesencephalic tissue into the striatum have provided evidence for long-term (up to 6 years) improvement in akinetic-rigid and axial symptoms.

We report on preliminary clinical results in two men (patient 1 aged 54, patient 2 aged 44 years) with Parkinson’s disease, Hoehn and Yahr stage V and III/IV, respectively, during defined off (12 h after drug withdrawal), who underwent stereo-tactic neurosurgery with implants of human embryonic tissue into putamen and caudate nucleus. Both patients have been evaluated monthly according to the Core Assessment Program for Intra-cerebral Transplantation for 12 and 8 months prior to surgery, respectively. In addition, F-dopa PET scans, structural and functional MR imaging, neuropsychological assessments, and personality scales were performed.

Patient 1 was operated bilaterally in one surgical session with implants of tissue from a total of seven donors at seven sites (five putamen, two caudate) per side. Patient 2 received tissue from four donors into the left striatum, and in a second surgical session 6 months later tissue from five donors into the right striatum (seven sites each, fivè putamen, two caudate). Both, embryonic tissue and patients were pretreated with lazaroids (tirilazad-mesylate) prior to transplantation, and lazaroid administration has been continued for 3 days after surgery. Immunosuppressive treatment for approximately 1 year from surgery was started 2 days before surgery and comprised cyclosporine (serum level 100 μg/l), azathioprine (100 mg/day) and corticosteroids (7.5 mg prednisolone/day).

Preliminary data of the clinical follow-up showed a marked to moderate improvement in overall motor performance and motor fluctuations that allowed a gradual reduction of levodopa medication. There were no adverse events or side effects due to neurosurgery. Patient 2 experienced a slight increase in physiological tremor, presumably due to immunosuppression.