Weight loss in Huntington disease increases with higher CAG repeat number.
Details
Serval ID
serval:BIB_225F26AE8B74
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Weight loss in Huntington disease increases with higher CAG repeat number.
Journal
Neurology
Working group(s)
EHDI Study Group
Contributor(s)
Zangerl A., Seppi K., Wenning G., Poewe W., Foeldy D., Auff E., Schober T., Wenzel K., Ott E., Walli J., Leblhuber F., Dürr A., Bloch F., Messouak O., Tallaksen C., Dubois B., Guillamo JS., Bachoud-Lévi AC., Engles A., Krystkowiak P., Destée A., Memin A., Thibaut-Tanchou S., Pasquier F., Azulay JP., Demonet JF., Galitzky M., Rascol O., Mollion H., Broussolle E., Madigand M., Lallement F., Goizet C., Tison F., Arguillère S., Viallet F., Bakchine S., Khoris J., Pages M., Camu W., Resch F., Hannequin D., Durif F., Saudeau D., Autret A., Andrich J., Saft C., Kraus PH., Przuntek H., Ecker D., Kramer B., Landwehrmeyer GB., Ludolph AC., Priller J., Meierkord H., Kuznik D., Dose M., Squitieri F., Albanese A., Abbruzzese G., Filla A., van de Warrenburg B., de Jong D., Kremer H., van Vugt J., Grimbergen Y., Roos R., Gawel M., Janik P., Kowalczys H., Pilczuk B., Kwiecinski H., Swiat M., Ochudło S., Modestowicz R., Niezgoda A., Łukasik M., Garcia de Yébenes J., García-Ruiz P., Martínez Descals A., Rojo A., Fontán A., Hernández J., Cantarero S., Fanjul S., Alegre J., Giménez Roldán S., Mateo D., Burguera JA., Solis P., Calopa M., Jaumà S., Bas J., Tolosa E., Muñoz JE., Gámez J., Cervera C., Zarranz JJ., Lezcano E., Gómez JC., Chacón J., Dinca L., Gamero MA., Redondo L., Castro A., Sesar A., López del Val J., López E., Ríos C., Castillio V., Burgunder JM., Nirkko A., Kälin A., Vingerhoets F., Wider C.
ISSN
1526-632X (Electronic)
ISSN-L
0028-3878
Publication state
Published
Issued date
2008
Volume
71
Number
19
Pages
1506-1513
Language
english
Notes
Publication types: Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
OBJECTIVE: Huntington disease (HD) is a hereditary neurodegenerative disorder caused by an expanded number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which is unknown. In order to elucidate the underlying mechanisms of weight loss in HD, we studied its relation to other disease characteristics including motor, cognitive, and behavioral disturbances and CAG repeat number.
METHODS: In 517 patients with early stage HD, we applied mixed-effects model analyses to correlate weight changes over 3 years to CAG repeat number and various components of the Unified Huntington's Disease Rating Scale (UHDRS). We also assessed the relation between CAG repeat number and body weight and caloric intake in the R6/2 mouse model of HD.
RESULTS: In patients with HD, mean body mass index decreased with -0.15 units per year (p < 0.001). However, no single UHDRS component, including motor, cognitive, and behavioral scores, was independently associated with the rate of weight loss. Patients with HD with a higher CAG repeat number had a faster rate of weight loss. Similarly, R6/2 mice with a larger CAG repeat length had a lower body weight, whereas caloric intake increased with larger CAG repeat length.
CONCLUSIONS: Weight loss in Huntington disease (HD) is directly linked to CAG repeat length and is likely to result from a hypermetabolic state. Other signs and symptoms of HD are unlikely to contribute to weight loss in early disease stages. Elucidation of the responsible mechanisms could lead to effective energy-based therapeutics.
METHODS: In 517 patients with early stage HD, we applied mixed-effects model analyses to correlate weight changes over 3 years to CAG repeat number and various components of the Unified Huntington's Disease Rating Scale (UHDRS). We also assessed the relation between CAG repeat number and body weight and caloric intake in the R6/2 mouse model of HD.
RESULTS: In patients with HD, mean body mass index decreased with -0.15 units per year (p < 0.001). However, no single UHDRS component, including motor, cognitive, and behavioral scores, was independently associated with the rate of weight loss. Patients with HD with a higher CAG repeat number had a faster rate of weight loss. Similarly, R6/2 mice with a larger CAG repeat length had a lower body weight, whereas caloric intake increased with larger CAG repeat length.
CONCLUSIONS: Weight loss in Huntington disease (HD) is directly linked to CAG repeat length and is likely to result from a hypermetabolic state. Other signs and symptoms of HD are unlikely to contribute to weight loss in early disease stages. Elucidation of the responsible mechanisms could lead to effective energy-based therapeutics.
Keywords
Adult, Aged, Animals, Body Mass Index, Body Weight, Disease Models, Animal, Energy Intake, Female, Humans, Huntington Disease/drug therapy, Huntington Disease/genetics, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Nerve Tissue Proteins/genetics, Nerve Tissue Proteins/metabolism, Neuroprotective Agents/therapeutic use, Nuclear Proteins/genetics, Nuclear Proteins/metabolism, Placebos, Riluzole/therapeutic use, Trinucleotide Repeats, Weight Loss/genetics
Pubmed
Web of science
Create date
24/09/2010 18:08
Last modification date
20/08/2019 12:59
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