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H D I N S I G H T S HD Research: France, cont... We obtained 31P spectra from our MRS protocol in the brain (Figure 2). Analysis of the 31P spectra in the time domain using jMRUI software allowed the quantification of energy metabolites ATP, Pi and PCr. The ratio of Pi/PCr was then calculated to determine the brain response to cortical activation. The Pi/PCr ratio has been linked to mitochondrial activation and it provides an index of mitochondrial oxidative regulation4. At rest, there was no significant difference in Pi/ PCr ratio between HD patients and control subjects. Visual stimulation allowed us to analyse the evolution of the Pi/PCr ratio in HD and control subjects. The Bonferroni-corrected Wilcoxon signed-rank test indicated an 11% increase in Pi/PCr ratio between rest and activation (P = 0.024), followed by a decrease between activation and recovery (P = 0.012) in controls (Figure 3). In contrast, no difference was found between the three stages for the HD group for Pi/PCr ratio (Figure 3). Figure 2: Representative 31P spectrum obtained at 3T with well-defined high-energy phosphate metabolites from the visual cortex of a control subject. Figure 3: Pi/PCr ratio before, during and after visual stimulation of 15 HD patients and 15 age- and sex-matched controls. Bonferroni-corrected Wilcoxon signedrank test indicated increased Pi/PCr between rest and activation (p = 0.024a) followed by a decrease between activation and recovery (p = 0.012b). No change was observed in patients (p > 0.05). Because the observed changes were relatively small, a subsequent study will allow us to further explore the use of Pi/ PCr ratio as an outcome measure in HD clinical trials. Recruiting patients from the previous study will allow us to test the reproducibility of the initial findings Mochel F, Charles P, Seguin F, et al. Early energy deficit in Huntington disease: identification of a plasma biomarker traceable during disease progression. PLoS ONE. 2007 Jul 25;2(7):e647. doi:10.1371/journal.pone.0000647. 1 in the same patient population and measure longitudinal changes. New patients at the early stage of the disease will also be recruited to validate our findings in an independent study population. In addition, we wish to include premanifest individuals to 3 Mochel F, Duteil S, Marelli C, et al. Dietary anaplerotic therapy improves peripheral tissue energy metabolism in patients with Huntington's disease. Eur J Hum Genet. 2010 Sep;18(9):1057-60. doi: 10.1038/ejhg.2010.72. Epub 2010 May 26. assess whether an abnormal brain energy profile can be identified before onset of overt HD symptoms, which is essential for development of future therapies. 4 Weiner DH, Fink LI, Maris J, et al. Abnormal skeletal muscle bioenergetics during exercise in patients with heart failure: role of reduced muscle blood flow. Circulation. 1986 Jun;73(6):1127-36. Mochel F, Haller RG. Energy deficit in Huntington disease: why it matters. J Clin Invest. 2011 Feb 1;121(2):493–499. doi: 10.1172/JCI45691. 2 HD Insights, Vol. 6 Copyright © Huntington Study Group 2013. All rights reserved. 9