Titre
Weight loss in Huntington disease increases with higher CAG repeat number.
Type
article
Institution
Externe
Périodique
Auteur(s)
Aziz, N.A.
Auteure/Auteur
van der Burg, J.M.
Auteure/Auteur
Landwehrmeyer, G.B.
Auteure/Auteur
Brundin, P.
Auteure/Auteur
Stijnen, T.
Auteure/Auteur
Roos, R.A.
Auteure/Auteur
Roos, R.A.
Auteure/Auteur
Contributrices/contributeurs
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.
Groupes de travail
EHDI Study Group
Liens vers les personnes
ISSN
1526-632X
Statut éditorial
Publié
Date de publication
2008
Volume
71
Numéro
19
Première page
1506
Dernière page/numéro d’article
1513
Langue
anglais
Notes
Publication types: Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
Sujets
PID Serval
serval:BIB_225F26AE8B74
PMID
Date de création
2010-09-24T17:08:36.019Z
Date de création dans IRIS
2025-05-20T19:11:08Z