Kordower, Halliday and Obeso reply:

We appreciate the opportunity to clarify a salient point in our recent review1. Drs. Isacson and Mendez are correct that the percentage of Lewy bodies in grafted neurons (5–8%) that we cited referred specifically to the findings of Kordower et al.2 and that it was not meant to refer to all of the papers referenced in the previous sentence. We are glad to clarify this point. It is interesting to note that Li et al.3 recently reported that 2% and 5% of grafted neurons contained Lewy bodies 12 and 15 years, respectively, after grafting, even though it is true that the cases reported by Mendez et al.4 contained far fewer Lewy bodies.

Hypotheses regarding why Lewy bodies form in long-term transplants have created great interest in the Parkinson's disease community, although nothing has yet been proven. Inflammation and oxidative stress are hypothesized to cause Parkinson's disease itself, and we would therefore not be surprised if these mechanisms have a role in the formation of Lewy bodies, although extensive microglial inflammation occurs in long-term striatal grafts in Huntington's disease patients without the formation of Lewy bodies5. We pointed out in our review that the significance of Lewy bodies in terms of cell death or protection is still uncertain. Accordingly, we agree with our colleagues that, given that Lewy bodies are relatively few in number, their contribution to and impact in grafted neurons may not be determinant factors for the success of cell replacement therapy, as pointed out elsewhere6. At the same time, the fact that some young transplanted cells do show the pathological hallmark of Parkinson's disease may signal a potential limitation of cell replacement and similar approaches7.