Clinical outcome of cotransplantation of peripheral nerve and adrenal medulla in patients with Parkinson's disease

Object. Transplants of adrenal medulla (AM) and fetal ventral mesencephalon (FVM) are currently being tested as therapeutic alternatives in patients w ith Parkinson's disease (PD). At the Clinica Puerta de Hierro in Madrid, a con trolled clinical trial is underway to establish which donor tissue, if any, is the best for open surgical implantation in patients with PD. Methods. Since 1987. varying degrees of clinical improvement have been achi eved in Grade IV and V parkinson lan patients by implanting perfused AM and FVM into the right caudate nucleus. To investigate further whether implant ation of different types of donor tissues results in qualitatively and quan titatively different degrees of recovery, four patients with Grade TV or V PD received implants of pre-coincubated autologous AM and intercostal nerve in the caudate nucleus. Four nonsurgically treated patients served as a co ntrol group. Three pears posttransplantation, longer on phases (46.2% +/- 1 0.4% of the day presurgery to 87.5% +/- 10.4% of the day 36 months postsurg ery) and improved symptoms in on and off phases persist in all four cases, with reduced dyskinesias (67.1% +/- 9.2% of the day in on phases presurgery to 17% +/- 13.8% of the day in on phases 36 months postsurgery). Progress appears to be stepwise, starting within weeks of tranplantation and becomin g clinically significant in the 2nd and 3rd months (similar to our AM- and sooner than in our FVM-implanted patients), followed by a period of stabili ty and, after a second wave of improvement 12 to 18 months posttransplantat ion (similar to FVM implants), has continued (87.5 +/- 7 points presurgery to 46 +/- 5.6 points 36 months postsurgery). In the experimental group, dos es of levodopa have been reduced by more than 60% and dopamine agonist use has not resumed. In contrast, there have been no significant clinical chang es in the control group. Conclusions. Implantation of tissue other than fetal tissue can promote a l ong-term improvement in the clinical symptomatology of seriously disabled p arkinsonian patients. This finding is supported by the autopsy report of a patient with PD who had undergone grafting of AM plus peripheral nerve in w hich it was demonstrated that a large number of tyrosine hydroxylase-positi ve cells survive I year after implantation. In addition, there was a dense network of host dopaminergic fibers around the graft.