A Plasma Biomarker

HD Lighthouse Contributing Editor's Comment: Through careful and rigorous research, the authors have identified another biomarker for disease progression and confirmed that there is a metabolic defect associated with Huntington's Disease.

Weight loss is common in Huntington's Disease and people with the disease often need extra calories to maintain their weight. One issue has been whether this is a result of a metabolic defect associated with the disease or whether it can be explained by the extra calories consumed by the choreic movements.

The researchers found lower levels of branched chain amino acids (BCAA).

This research is important for two reasons, first because we need biomarkers, and secondly, because it helps to clarify the role of defects in energy metabolism in Huntington's Disease so rational treatments can be developed.

It is critical for researchers to find and validate biomarkers. First we need to reduce clinical trial time so that treatments can get to patients sooner. Currently the United Huntington's Disease Rating Scale is used to measure progression. This scale depends upon clinical assessment of the individual. Since progression is slow in HD, it can require years to detect significant differences between the treatment group and the control group. Second, we need to include those who are gene positive who have not reached clinical onset in clinical trials; biomakers of changes which begin to occur before clinical onset will be needed to assess whether the treatment is effective. Finally, when treatments become available, biomakers may be used to identify when gene carriers should start taking them.

To read the full study go here: http://www.plosone.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.pone.0000647

-- Marsha L. Miller, Ph.D.
Posted to the HDL: 07-28-2007

Researchers are filling in the puzzle pieces about energy metabolism in HD.

Early Energy Deficit in Huntington Disease: Identification of a Plasma Biomarker Traceable during Disease Progression

Fanny Mochel, Perrine Charles, François Seguin, Julie Barritault, Christiane Coussieu, Laurence Perin, Yves Le Bouc, Christiane Gervais, Guislaine Carcelain, Anne Vassault, Josué Feingold, Daniel Rabier, Alexandra Durr

Huntington disease (HD) is a fatal neurodegenerative disorder, with no effective treatment. The pathogenic mechanisms underlying HD has not been elucidated, but weight loss, associated with chorea and cognitive decline, is a characteristic feature of the disease that is accessible to investigation. We, therefore, performed a multiparametric study exploring body weight and the mechanisms of its loss in 32 presymptomatic carriers and HD patients in the early stages of the disease, compared to 21 controls. We combined this study with a multivariate statistical analysis of plasma components quantified by proton nuclear magnetic resonance ((1)H NMR) spectroscopy.

We report evidence of an early hypermetabolic state in HD. Weight loss was observed in the HD group even in presymptomatic carriers, although their caloric intake was higher than that of controls. Inflammatory processes and primary hormonal dysfunction were excluded. (1)H NMR spectroscopy on plasma did, however, distinguish HD patients at different stages of the disease and presymptomatic carriers from controls.

This distinction was attributable to low levels of the branched chain amino acids (BCAA), valine, leucine and isoleucine. BCAA levels were correlated with weight loss and, importantly, with disease progression and abnormal triplet repeat expansion size in the HD1 gene. Levels of IGF1, which is regulated by BCAA, were also significantly lower in the HD group. Therefore, early weight loss in HD is associated with a systemic metabolic defect, and BCAA levels may be used as a biomarker, indicative of disease onset and early progression. The decreased plasma levels of BCAA may correspond to a critical need for Krebs cycle energy substrates in the brain that increased metabolism in the periphery is trying to provide.

Source: PlOs One 2007 Jul 25;2:e647.