Clinical neurotransplantation: core assessment protocol rather than sham surgery as control.
Basic neurotransplantation research evoked clinical trials of restorative brain surgery. Parkinson's disease was the first and primary test bed for this putative new therapeutic method. Various centers performed the grafting surgery and the behavioral evaluations in different ways, and observed a varying degree of symptomatic relief. This led to a plea for double blind placebo-controlled clinical trials, which have since been performed and of which the first outcomes were recently published. In the present paper this approach of experimental neurotransplantation in brain diseases is discussed and rejected. Neural grafting in the central nervous system is irreversible and is therefore not suitable for experimental approaches originally designed for and best suited to drug studies. For Parkinson's disease in particular, the technique is far from optimized to perform large-scale studies at this stage. Moreover, previous negative results of adrenal medulla tissue implantation in the brain of patients make placebo effects rather unlikely. Moral arguments concerning the validity of the informed consent, therapeutic misconception, and the risk/benefit ratio can be added in the plea against this control surgery. Finally, a recommendation is made for study designs that apply a disease-dedicated core assessment protocol (CAP) that can evaluate the period from pre-operative to post-convalescent stages quantitatively, and therefore, unbiased. The strength of these CAPs is that they allow comparisons of different grafting techniques, of results between centers and of other types of interventions and invasive treatments such as deep brain stimulation. On ethical grounds, it is unacceptable not to use a study design that circumvents sham or imitation surgery. It is a challenge for the neuroscience community to develop CAPs for brain diseases that are eligible for neurotransplantation in the future.
Boer
Gerard J
GJ
Graduate School Neurosciences Amsterdam, Netherlands Institute for Brain Research, Amsterdam, The Netherlands. g.boer@nih.knaw.nl
Widner
Håkan
H
D000313:Adrenal Medulla / Q000637:transplantation; D000818:Animals; D016380:Brain Tissue Transplantation / Q000941:ethics / Q000379:methods*; D002986:Clinical Trials as Topic / Q000941:ethics / Q000379:methods; D016332:Fetal Tissue Transplantation / Q000941:ethics / Q000379:methods; D006801:Humans; D010300:Parkinson Disease / Q000601:surgery*; D018579:Patient Selection / Q000941:ethics; D010919:Placebos / Q000627:therapeutic use*; D014182:Transplantation, Autologous
D010919:Placebos