Patient selection

The Parkinson's-Reversing Breakthrough

Treatment for Parkinson Disease

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Patient selection is an important factor in the design of transplantation studies. It is obviously important to ensure the correct diagnosis, and most groups utilize the UK brain bank criteria in order to minimize the risk of an atypical Parkinsonism. There is no evidence to suggest that fetal nigral transplantation will benefit patients with atypical Parkinsonism where degeneration occurs in the striatum and pallidum and likely precludes any benefit from restoration of the nigro-striatal system. Freed et al. suggest that transplantation is more effective in younger patients who respond well to levodopa, possibly because there is less degeneration of non-dopaminergic systems and transplant has a better chance of improving patient disability (Freed et al., 2001). Olanow et al. did not find an age effect, but observed significant benefits with transplantation in the subset of patients with milder disease, possibly reflecting the same phenomenon (Olanow et al., 2003). Interestingly, several studies have reported that patients who do best following transplantation are receiving relatively lower doses of levodopa than those who do poorly (Wenning et al., 1997; Hagell et al., 1999; Brundin et al., 2000a). This observation is consistent with the notion that the patients who do best with transplantation have relatively mild disease. More advanced patients who require higher levodopa doses may benefit less, possibly because of involvement of non-dopaminergic regions (Lang and Obeso, 2004a). To this point, studies in the 6-OHDA model in the rat similarly note greater benefits with intrastriatal transplantation in animals that have lesions confined to the striatum in comparison to those with lesions involving both striatal and non-striatal forebrain dopaminergic projections (Kirik et al., 2001). Longer periods of follow-up may also be required to see the full benefits of transplantation. Freed et al. noted continued improvement over 3 years, although observations during the last 2 years were unblinded. Additionally, late improvement in physiologic measures of motor performance and a delay in recovery in movement-related cortical function have been reported (Brundin et al., 2000a; Gordon et al., 2004). Collectively, these observations suggest that the best candidates for fetal nigral transplantation and other cell-based therapies might be younger PD patients with relatively mild disease who respond well to levodopa and have minimal or no evidence of non-dopaminergic lesions.

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