OBJECTIVE: To evaluate whether striatal [(18)F]MNI-659 PET imaging of phosphodiesterase 10A (PDE10) serves as a sensitive and reliable biomarker of striatal neurodegeneration in a longitudinal cohort of participants with early Huntington disease (HD). METHODS: A cohort of participants with HD, including both participants premanifest or manifest with motor signs, underwent clinical assessments, genetic determination, and 2 [(18)F]MNI-659 PET imaging sessions approximately 1 year apart. Eleven healthy control (HC) participants underwent clinical assessments and [(18)F]MNI-659 PET imaging once. Striatal binding potentials (BPnd) were estimated for brain regions of interest, specifically within the basal ganglia, and compared between baseline and follow-up imaging. Clinical measures of HD severity were assessed at each visit. RESULTS: Eight participants with HD (6 manifest; 2 premanifest) participated. Of those with manifest HD, all had relatively early stage disease (stage 1, n = 2; stage 2, n = 4) and a Unified Huntington's Disease Rating Scale total motor score <45. As expected, the HD cohort as a whole had a reduction in the basal ganglia BPnd to approximately 50% of that seen in HC. On follow-up scans, [(18)F]MNI-659 uptake declined in the putamen and caudate nucleus in all 8 participants. The mean annualized rates of decline in signal in the caudate, putamen, and globus pallidus and the putamen were 16.6%, 6.9%, and 5.8%, respectively. In HC, the annualized reduction in signal in striatal regions was less than 1%. CONCLUSION: Longitudinal data in this small cohort of participants with early HD support [(18)F]MNI-659 PET imaging of PDE10 as a useful biomarker to track HD disease progression.
OBJECTIVE: To evaluate whether striatal [(18)F]MNI-659 PET imaging of phosphodiesterase 10A (PDE10) serves as a sensitive and reliable biomarker of striatal neurodegeneration in a longitudinal cohort of participants with early Huntington disease (HD). METHODS: A cohort of participants with HD, including both participants premanifest or manifest with motor signs, underwent clinical assessments, genetic determination, and 2 [(18)F]MNI-659 PET imaging sessions approximately 1 year apart. Eleven healthy control (HC) participants underwent clinical assessments and [(18)F]MNI-659 PET imaging once. Striatal binding potentials (BPnd) were estimated for brain regions of interest, specifically within the basal ganglia, and compared between baseline and follow-up imaging. Clinical measures of HD severity were assessed at each visit. RESULTS: Eight participants with HD (6 manifest; 2 premanifest) participated. Of those with manifest HD, all had relatively early stage disease (stage 1, n = 2; stage 2, n = 4) and a Unified Huntington's Disease Rating Scale total motor score <45. As expected, the HD cohort as a whole had a reduction in the basal ganglia BPnd to approximately 50% of that seen in HC. On follow-up scans, [(18)F]MNI-659 uptake declined in the putamen and caudate nucleus in all 8 participants. The mean annualized rates of decline in signal in the caudate, putamen, and globus pallidus and the putamen were 16.6%, 6.9%, and 5.8%, respectively. In HC, the annualized reduction in signal in striatal regions was less than 1%. CONCLUSION: Longitudinal data in this small cohort of participants with early HD support [(18)F]MNI-659 PET imaging of PDE10 as a useful biomarker to track HD disease progression.
Authors: Bryan Zeitler; Steven Froelich; Kimberly Marlen; David A Shivak; Qi Yu; Davis Li; Jocelynn R Pearl; Jeffrey C Miller; Lei Zhang; David E Paschon; Sarah J Hinkley; Irina Ankoudinova; Stephen Lam; Dmitry Guschin; Lexi Kopan; Jennifer M Cherone; Hoang-Oanh B Nguyen; Guijuan Qiao; Yasaman Ataei; Matthew C Mendel; Rainier Amora; Richard Surosky; Josee Laganiere; B Joseph Vu; Anand Narayanan; Yalda Sedaghat; Karsten Tillack; Christina Thiede; Annette Gärtner; Seung Kwak; Jonathan Bard; Ladislav Mrzljak; Larry Park; Taneli Heikkinen; Kimmo K Lehtimäki; Marie M Svedberg; Jenny Häggkvist; Lenke Tari; Miklós Tóth; Andrea Varrone; Christer Halldin; Andrea E Kudwa; Sylvie Ramboz; Michelle Day; Jyothisri Kondapalli; D James Surmeier; Fyodor D Urnov; Philip D Gregory; Edward J Rebar; Ignacio Muñoz-Sanjuán; H Steve Zhang Journal: Nat Med Date: 2019-07-01 Impact factor: 53.440
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