Weight loss in Huntington disease increases with higher CAG repeat number

Autor: Aziz, Na, van der Burg, Jm, Landwehrmeyer, Gb, Brundin, P, Stijnen, T, Ehdi, Sg, Roos, Ra, 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, Ludolph, Ac, Priller, J, Meierkord, H, Kuznik, D, Dose, M, Squitieri, F, Albanese, A, Abbruzzese, Giovanni, 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.
Přispěvatelé: N. A., Aziz, J. M., M, G. B., Landwehrmeyer, P., Brundin, T., Stijnen, E. H. D., R. A. C., Filla, Alessandro
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Male
Pathology
therapeutic use
Nuclear Protein
Neurology
Disease
Body Mass Index
Placebos
Mice
Degenerative disease
Trinucleotide Repeats
Weight loss
genetics
Huntingtin Protein
Riluzole
Nuclear Proteins
Middle Aged
Huntington Disease
Neuroprotective Agents
Inbred C57BL
Mice
genetics/metabolism
Placebos
Riluzole
Female
medicine.symptom
Psychology
Adult
congenital
hereditary
and neonatal diseases and abnormalities
medicine.medical_specialty
Mice
Transgenic
Nerve Tissue Proteins
Animal
Energy Intake
Female
Humans
Huntington Disease
Central nervous system disease
therapeutic use
Trinucleotide Repeats
Weight Lo
Internal medicine
Weight Loss
mental disorders
medicine
Animals
Humans
Hereditary Neurodegenerative Disorder
Transgenic
Middle Aged
Nerve Tissue Protein
Aged
drug therapy/genetics/physiopathology
Male
Mice
Mice
Body Weight
medicine.disease
Adult
Aged
Animals
Body Mass Index
Body Weight
Disease Model
Mice
Inbred C57BL
Disease Models
Animal
Endocrinology
genetics/metabolism
Neuroprotective Agent
Neurology (clinical)
Energy Intake
Body mass index
Popis: 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.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.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.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.
Databáze: OpenAIRE
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