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Image: Scaled fitted spline curves of key variables plotted over CAP D (CAG-corrected age). Blue colors indicate variables that decrease and red colors indicate variables that increase. Vertical axis is in standard deviation (SD) units. TMS indicates total motor score; CSF, cerebral spinal fluid; DYS, dysrhythmia; O–C, obsessive– compulsive; SDMT, Symbol Digit Modalities Test; SMELL, University of Pennsylvania Smell Identification Test (UPSIT); TFC, total functional capacity. Copyright © Huntington Study Group 2014. All rights reserved. HTRF analysis of soluble huntingtin in PHAROS PBMCs Neurology. 2013 Sep 24;81(13):1134-40. doi: 10.1212/WNL.0b013e3182a55ede. Epub 2013 Aug 21. By: Moscovitch-Lopatin M, Goodman RE, Eberly S, Ritch JJ, Rosas HD, Matson S, Matson W, Oakes D, Young AB, Shoulson I, Hersch SM; Huntington Study Group PHAROS Investigators (Summary by Steven M. Hersch, MD, PhD and Miriam Moscovitch-Lopatin, PhD, PMP) Mutant huntingtin (mHTT) is a target of many treatments currently being developed for HD. Therefore, the ability to measure levels of mHTT in humans will be crucial to future research efforts. Measuring mHTT has been very technically challenging. In our study of white blood cell samples from the PHAROS study, we used a sophisticated fluorescent assay to detect higher relative values of soluble mHTT in gene carriers (CAG≥37) prior to symptoms, and relatively lower values in symptomatic HD subjects. The study demonstrated that soluble mHTT can be usefully detected in blood, and that HD may influence its levels. Since then, we have used this same assay in blood from early HD subjects participating in the HSG's Reach2HD trial of PBT2 (PRANA Biotechnology), and found that the treatment can affect soluble mHTT levels. Currently, we are developing an assay that can also measure mHTT aggregates in clinical samples, which we believe will also prove useful for developing treatments that target huntingtin. Image: Ratio of mHTT to dsDNA in different groups of HD gene carriers and health controls. Levels of soluble mHTT in white blood cells were elevated in premanifest HD and diminished in individuals with symptomatic HD. Research Round-Up: Insights, cont... Clinical and biomarker changes in premanifest Huntington disease show trial feasibility: A decade of the PREDICT-HD study, cont… Source: Figure and caption as originally published in Paulsen JS, Long JD, Johnson HJ, Aylward EH, et al; PREDICT-HD investigators and coordinators of the Huntington Study Group. Clinical and biomarker changes in premanifest Huntington disease show trial feasibility: A decade of the PREDICT-HD study. Front Aging Neurosci. 2014; 6: 78. Published online Apr 22, 2014. doi: 10.3389/fnagi.2014.00078 H D I N S I G H T S HD Insights, Vol. 9 8