Collagen XIX Alpha 1 Improves Prognosis in Amyotrophic Lateral Sclerosis.

Autor: Calvo AC; 1LAGENBIO (Laboratory of Genetics and Biochemistry), Faculty of Veterinary-IIS, IA2-CITA, University of Zaragoza, Zaragoza, Spain., Cibreiro GA; 2Neurology Department, ALS Unit, CIBERER U-723, Health Research Institute, October 12th Hospital 'IIS I+12', Madrid, Spain., Merino PT; 2Neurology Department, ALS Unit, CIBERER U-723, Health Research Institute, October 12th Hospital 'IIS I+12', Madrid, Spain., Roy JF; 3Ferkauf Graduate School of Psychology, Yeshiva University, NY 10461, USA., Galiana A; 4Servicio de Reumatología, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria La Princesa, Madrid, Spain., Rufián AJ; 2Neurology Department, ALS Unit, CIBERER U-723, Health Research Institute, October 12th Hospital 'IIS I+12', Madrid, Spain., Cano JM; 5Orthopaedic Surgery Department, October 12th Hospital, Madrid, Spain., Martín MA; 6Grupo Enfermedades Mitocondriales y Neuromusculares, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), U723-CIBERER, Madrid, España., Moreno L; 1LAGENBIO (Laboratory of Genetics and Biochemistry), Faculty of Veterinary-IIS, IA2-CITA, University of Zaragoza, Zaragoza, Spain., Larrodé P; 1LAGENBIO (Laboratory of Genetics and Biochemistry), Faculty of Veterinary-IIS, IA2-CITA, University of Zaragoza, Zaragoza, Spain., Vázquez PC; 2Neurology Department, ALS Unit, CIBERER U-723, Health Research Institute, October 12th Hospital 'IIS I+12', Madrid, Spain., Galán L; 7Neurology Department, ALS Unit, Clínico Universitario San Carlos Hospital, Madrid, Spain., Mora J; 8Neurology Department, ALS Unit, Carlos III Hospital, Madrid, Spain., Muñoz-Blanco JL; 9Neurology Department, ALS Unit, Health Research Institute, Gregorio Marañón Hospital 'IISGM', Madrid, Spain., Muñoz MJ; 1LAGENBIO (Laboratory of Genetics and Biochemistry), Faculty of Veterinary-IIS, IA2-CITA, University of Zaragoza, Zaragoza, Spain., Zaragoza P; 1LAGENBIO (Laboratory of Genetics and Biochemistry), Faculty of Veterinary-IIS, IA2-CITA, University of Zaragoza, Zaragoza, Spain., Pegoraro E; 10Neurological Clinic, Department of Neurosciences, University of Padova, Padova, Italy., Sorarù G; 10Neurological Clinic, Department of Neurosciences, University of Padova, Padova, Italy., Mora M; 11Muscle Cell Biology Laboratory, Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy., Lunetta C; 12NEMO (NEuroMuscular Omnicentre) Clinical Center, Fondazione Serena Onlus, Milan, Italy., Penco S; 13Medical Genetics Unit, Department of Laboratory Medicine, Niguarda Ca' Granda Hospital, Milan, Italy., Tarlarini C; 13Medical Genetics Unit, Department of Laboratory Medicine, Niguarda Ca' Granda Hospital, Milan, Italy., Esteban J; 2Neurology Department, ALS Unit, CIBERER U-723, Health Research Institute, October 12th Hospital 'IIS I+12', Madrid, Spain., Osta R; 1LAGENBIO (Laboratory of Genetics and Biochemistry), Faculty of Veterinary-IIS, IA2-CITA, University of Zaragoza, Zaragoza, Spain., Redondo AG; 2Neurology Department, ALS Unit, CIBERER U-723, Health Research Institute, October 12th Hospital 'IIS I+12', Madrid, Spain.
Jazyk: angličtina
Zdroj: Aging and disease [Aging Dis] 2019 Apr 01; Vol. 10 (2), pp. 278-292. Date of Electronic Publication: 2019 Apr 01 (Print Publication: 2019).
DOI: 10.14336/AD.2018.0917
Abstrakt: The identification of more reliable diagnostic or prognostic biomarkers in age-related neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS), is urgently needed. The objective in this study was to identify more reliable prognostic biomarkers of ALS mirroring neurodegeneration that could be of help in clinical trials. A total of 268 participants from three cohorts were included in this study. The muscle and blood cohorts were analyzed in two cross-sectional studies, while the serial blood cohort was analyzed in a longitudinal study at 6-monthly intervals. Fifteen target genes and fourteen proteins involved in muscle physiology and differentiation, metabolic processes and neuromuscular junction dismantlement were studied in the three cohorts. In the muscle biopsy cohort, the risk for a higher mortality in an ALS patient that showed high Collagen type XIX, alpha 1 (COL19A1) protein levels and a fast progression of the disease was 70.5% ( P < 0.05), while in the blood cohort, this risk was 20% ( P < 0.01). In the serial blood cohort, the linear mixed model analysis showed a significant association between increasing COL19A1 gene levels along disease progression and a faster progression during the follow-up period of 24 months ( P < 0.05). Additionally, higher COL19A1 levels and a faster progression increased 17.9% the mortality risk ( P < 0.01). We provide new evidence that COL19A1 can be considered a prognostic biomarker that could help the selection of homogeneous groups of patients for upcoming clinical trial and may be pointed out as a promising therapeutic target in ALS.
Databáze: MEDLINE