Your browser doesn't support javascript.
loading
Prospective natural history study of C9orf72 ALS clinical characteristics and biomarkers.
Cammack, Alexander J; Atassi, Nazem; Hyman, Theodore; van den Berg, Leonard H; Harms, Matthew; Baloh, Robert H; Brown, Robert H; van Es, Michael A; Veldink, Jan H; de Vries, Balint S; Rothstein, Jeffrey D; Drain, Caroline; Jockel-Balsarotti, Jennifer; Malcolm, Amber; Boodram, Sonia; Salter, Amber; Wightman, Nicholas; Yu, Hong; Sherman, Alexander V; Esparza, Thomas J; McKenna-Yasek, Diane; Owegi, Margaret A; Douthwright, Catherine; McCampbell, Alexander; Ferguson, Toby; Cruchaga, Carlos; Cudkowicz, Merit; Miller, Timothy M.
Afiliación
  • Cammack AJ; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Atassi N; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Hyman T; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • van den Berg LH; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Harms M; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Baloh RH; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Brown RH; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • van Es MA; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Veldink JH; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • de Vries BS; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Rothstein JD; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Drain C; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Jockel-Balsarotti J; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Malcolm A; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Boodram S; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Salter A; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Wightman N; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Yu H; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Sherman AV; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Esparza TJ; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • McKenna-Yasek D; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Owegi MA; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Douthwright C; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • McCampbell A; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Ferguson T; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Cruchaga C; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Cudkowicz M; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
  • Miller TM; From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Depar
Neurology ; 93(17): e1605-e1617, 2019 10 22.
Article en En | MEDLINE | ID: mdl-31578300
ABSTRACT

OBJECTIVE:

To define the natural history of the C9orf72 amyotrophic lateral sclerosis (C9ALS) patient population, develop disease biomarkers, and characterize patient pathologies.

METHODS:

We prospectively collected clinical and demographic data from 116 symptomatic C9ALS and 12 non-amyotrophic lateral sclerosis (ALS) full expansion carriers across 7 institutions in the United States and the Netherlands. In addition, we collected blood samples for DNA repeat size assessment, CSF samples for biomarker identification, and autopsy samples for dipeptide repeat protein (DPR) size determination. Finally, we collected retrospective clinical data via chart review from 208 individuals with C9ALS and 450 individuals with singleton ALS.

RESULTS:

The mean age at onset in the symptomatic prospective cohort was 57.9 ± 8.3 years, and median duration of survival after onset was 36.9 months. The monthly change was -1.8 ± 1.7 for ALS Functional Rating Scale-Revised and -1.4% ± 3.24% of predicted for slow vital capacity. In blood DNA, we found that G4C2 repeat size correlates positively with age. In CSF, we observed that concentrations of poly(GP) negatively correlate with DNA expansion size but do not correlate with measures of disease progression. Finally, we found that size of poly(GP) dipeptides in the brain can reach large sizes similar to that of their DNA repeat derivatives.

CONCLUSIONS:

We present a thorough investigation of C9ALS natural history, providing the basis for C9ALS clinical trial design. We found that clinical features of this genetic subset are less variant than in singleton ALS. In addition, we identified important correlations of C9ALS patient pathologies with clinical and demographic data.
Asunto(s)
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteína C9orf72 / Esclerosis Amiotrófica Lateral Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Neurology Año: 2019 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteína C9orf72 / Esclerosis Amiotrófica Lateral Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Neurology Año: 2019 Tipo del documento: Article