Huntington's disease progression PET and clinical observations

Using serial [C-11]SCH 23390- and [C-11]raclopride-PET, we have measured th e rate of loss of striatal dopamine D1 and D2 receptor binding over a mean of 40 months in nine asymptomatic adult Huntington's disease mutation carri ers, four patients with symptomatic disease, seven mutation-negative contro ls and three subjects at risk for the disease. Eight of the nine asymptomat ic Huntington's disease mutation carriers had serial [C-11]raclopride-PET a nd showed a mean annual loss of striatal D2 binding of 4,0%, Only five of t hese eight, however, showed active progression, and they had a mean annual loss of D2 binding of 6.5 %, All nine asymptomatic mutation carriers had se rial [C-11]SCH 23390-PET and showed a mean annual loss of striatal DI bindi ng of 2,0%, Four of these subjects demonstrated active progression and they had a mean annual loss of 4,5%, Our four symptomatic Huntington's disease patients showed a mean annual loss of D2 binding of 3.0% and of D1 binding of 5,0%, Loss of striatal D1 and D2 binding was significantly greater in th e known mutation carriers than in the combined at-risk and gene-negative gr oups (P < 0,05), At follow-up PET all subjects were clinically assessed usi ng the Unified Huntington's Disease Rating Scale. Scores for motor function and total functional capacity correlated with PET measures of striatal dop amine receptor binding both in the asymptomatic mutation carriers (D1, P < 0.01) and across the combined asymptomatic and clinically affected Huntingt on's disease mutation carrier group (D1 and D2, P < 0,001), We conclude tha t PET measures of striatal D1 and D2 dopamine binding can be used to identi fy asymptomatic Huntington's disease mutation carriers who are actively pro gressing and who would thus be suitable for putative neuroprotective therap ies. Measures of disease progression rates in Huntington's disease patients and asymptomatic mutation carriers will be of critical importance in futur e trials of experimental restorative treatments.