Multiple Sclerosis

Group leader: David Otaegui, Ph.D.

Biodonostia HRI david.otaegui@biodonostia.org

Strategic Objectives

  • Epidemiological register of multiple sclerosis.
  • Genetic association studies.
  • Understanding how attacks and remyelination occur. Characterisation of the transcriptome and its regulation by means of microRNA in the different stages of a disease.
  • Studies of the involvement of microparticles on MS.
  • Development of prognostic markers (gene expression, neuroimaging, biochemistry and immunology) and treatment markers.

Main lines of research

From the beginning, we have focused our research on DNA analysis in order to search for susceptibility polymorphisms which may have an influence on the risk of suffering a disease, or on the progression of the disease in question. The natural evolution of these lines of research has led us to focus more specifically on gene expression (RNA and protein) in an attempt to understand the etiology of the disease and to search for prognostic factors (biomarkers) in the blood which may help to anticipate and/or characterise the different stages of MS (attack versus non-attack).

  • Study of the factors involved in remyelination. Analysis of expression patterns on all RNA and microRNA in patients’ blood.
  • Search for outbreak biomarkers and possible treatment biomarkers.
  • Study of potential biomarkers and the biological impact of microparticles circulating in peripheral blood.
  • Validation of susceptibility SNPs.
  • Study of family aggregations.
  • Study of OCBs.
  • Potential effect of vitamin D as a co-treatment for MS.
  • Clinical characterisation of patients in the province of Gipuzkoa.

Team Members

Name Surname
Center E-mail
Ainhoa Alberro Garitano Biodonostia HRI ainhoa.alberro@biodonostia.org
Maialen Arruti Gonzalez Donostialdea IHO maialen.arrutigonzalez@osakidetza.eus
Tamara Castillo Triviño Goierri – Alto Urola IHO
Ioana Marcela Croitoru Donostialdea IHO  ioana.croitoru@biodonostia.org
Leire Iparraguirre Gil Biodonostia HRI leire.iparraguirre@biodonostia.org
Itziar Lopetegui Larruscain Donostialdea IHO itziar.lopetegilarruskain@osakidetza.eus
Laura Moles Alegre Biodonostia HRI laura.moles@biodonostia.org
Maider Muñoz Culla Biodonostia HRI maider.munoz@biodonostia.org
Iñaki Osorio Querejeta Biodonostia HRI inaki.osorio@biodonostia.org
Alvaro Prada Iñurrategui Donostialdea IHO alvarojose.pradainurrategui@osakidetza.eus
Lucia Elena Sepúlveda Sánchez Biodonostia HRI lucia.sepulveda@biodonostia.org

Scientific Output

Originals

Published: 10 / 75

Lipid-Specific Immunoglobulin M Bands in Cerebrospinal Fluid Are Associated with a Reduced Risk of Developing Progressive Multifocal Leukoencephalopathy during Treatment with Natalizumab.

Villar LM, Costa-Frossard L, Masterman T, Fernandez O, Montalban X, Casanova B, Izquierdo G, Coret F, Tumani H, Saiz A, Arroyo R, Fink K, Leyva L, Espejo C, Simo-Castello M, Garcia-Sanchez MI, Lauda F, Llufriu S, Alvarez-Lafuente R, Olascoaga J, Prada A, Oterino A, de Andres, C, Tintore M, Ramio-Torrenta L, Rodriguez-Martin E, Picon, Comabella C, Quintana M, Agueera E, Diaz E, Fernandez-Bolanos S, Garcia-Merino R, Landete JA, Menendez-Gonzalez L, Navarro M, Perez L, Sanchez-Lopez D, Serrano-Castro F, Tunon PJ, Espino A, Muriel M, Bar-Or A, Alvarez-Cermeno JC.

Ann. Neurol. 2015; 77: 447-457. FI: 9.977 (Q1).

A functional variant that affects exon-skipping and protein expression of SP140 as genetic mechanism predisposing to multiple sclerosis.

Matesanz F, Potenciano V, Fedetz M, Ramos-Mozo P, del Mar Abad-Grau M, Karaky M, Barrionuevo C, Izquierdo G, Ruiz-Pena JL, Garcia-Sanchez MI, Lucas M, Fernandez O, Leyva L, Otaegui D, Munoz-Culla M, Olascoaga J, Vandenbroeck K, Alloza I, Astobiza I, Antigueedad A, Villar LM, Alvarez-Cermeno JC, Malhotra S, Comabella M, Montalban X, Saiz A, Blanco Y, Arroyo R, Varade J, Urcelay E, Alcina A.

Hum. Mol. Genet. 2015; 24: 5619-5627. FI: 6.393 (Q1).

Genome-wide significant association of ANKRD55 rs6859219 and multiple sclerosis risk.

Lill CM, Schjeide BMM, Graetz C, Liu T, Damotte V, Akkad DA, Blaschke P, Gerdes LA, Kroner A, Luessi F, Cournu-Rebeix I, Hoffjan S, Winkelmann A, Touze E, Pico F, Corcia P, Otaegui D, Antigueedad A, Alcina A, Comabella M, Montalban X, Olascoaga J, Matesanz F, Doerner T, Li SC, Steinhagen-Thiessen E, Lindenberger U, Chan A, Rieckmann P, Hartung HP, Aktas O, Lohse P, Buttmann M, Kuempfel T, Kubisch C, Zettl UK, Epplen JT, Fontaine B, Zipp F, Vandenbroeck K, Bertram L.

J. Med. Genet. 2013; 50: 140-143. FI: 5.703 (Q1).

Identification of a functional variant in the KIF5A-CYP27B1-METTL1-FAM119B locus associated with multiple sclerosis.

Alcina A, Fedetz M, Fernandez O, Saiz A, Izquierdo G, Lucas M, Leyva L, Garcia-Leon JA, del Mar Abad-Grau M, Alloza I, Antigueedad A, Garcia-Barcina MJ, Vandenbroeck K, Varade J, de la Hera B, Arroyo R, Comabella M, Montalban X, Petit-Marty N, Navarro A, Otaegui D, Olascoaga J, Blanco Y, Urcelay E, Matesanz F.

J. Med. Genet. 2013; 50: 25-33. FI: 5.703 (Q1).

Blood miRNA expression pattern is a possible risk marker for natalizumab-associated progressive multifocal leukoencephalopathy in multiple sclerosis patients.

Munoz-Culla M, Irizar H, Castillo-Trivino T, Saenz-Cuesta M, Sepulveda L, Lopetegi I, Lopez de Munain A, Olascoaga J, Baranzini SE, Otaegui D.

Mult. Scler. J. 2014; 20: 1851-1859. FI: 4.863 (Q1).

Antibodies to MOG and AQP4 in adults with neuromyelitis optica and suspected limited forms of the disease.

Höftberger R, Sepulveda M, Armangue T, Blanco Y, Rostásy K, Cobo Calvo A, Olascoaga J, Ramió-Torrentà L, Reindl M, Benito-León J, Casanova B, Arrambide G, Sabater L, Graus F, Dalmau J, Saiz A.

Mult. Scler. J. 2015; 21: 866-874. FI: 4.822 (Q1).

Analysis of prognostic factors associated with longitudinally extensive transverse myelitis.

Sepulveda M, Blanco Y, Rovira A, Rio J, Mendibe M, Llufriu S, Gabilondo I, Villoslada P, Castillo J, Corral J, Ayuso T, Iniguez C, Santos S, Guijarro C, Ramio-Torrenta L, Sempere AP, Olascoaga J, Graus F, Montalban X, Saiz A.

Mult. Scler. J. 2013; 19: 742-748. FI: 4.472 (Q1).

Replication study of 10 genes showing evidence for association with multiple sclerosis: validation of TMEM39A, IL12B and CLBL genes.

Varade J, Comabella M, Ortiz MA, Arroyo R, Fernández O, Pinto-Medel J, Fedetz M, Izquierdo G, Lucas M, López Gómez C, Catalá Rabasa A, Alcina A, Matesanz F, Alloza I, Antigüedad A, García-Barcina M, Otaegui D, Olascoaga J, Saiz A, Blanco Y, Montalban X, Vandenbroeck K, Urcelay E.

Mult. Scler. J. 2012; 18: 959-965. FI: 4.255 (Q1).

HLA-DRB1*15:01 and multiple sclerosis: a female association?

Irizar H, Muñoz-Culla M, Zuriarrain O, Goyenechea E, Castillo-Trivino T, Prada A, Sáenz-Cuesta M, De Juan D, López de Munain A, Olascoaga J, Otaegui D.

Mult. Scler. J. 2012; 18: 569-577. FI: 4.255 (Q1).

Chitinase 3-like 1 plasma levels are increased in patients with progressive forms of multiple sclerosis.

Canto E, Reverter F, Morcillo-Suarez C, Matesanz F, Fernández O, Izquierdo G, Vandenbroeck K, Rodríguez-Antigüedad A, Urcelay E, Arroyo R, Otaegui D, Olascoaga J, Saiz A, Navarro A, Sánchez A, Domínguez C, Caminero A, Horga A, Tintore M, Montalban X, Comabella M.

Mult. Scler. J. 2012; 18: 983-990. FI: 4.255 (Q1).

Reviews

Published: 10 / 10

Rituximab in Relapsing and Progressive Forms of Multiple Sclerosis: A Systematic Review.

Castillo-Trivino T, Braithwaite D, Bacchetti P, Waubant E.

PLoS One. 2013; 8: e66308. FI: 3.730 (Q1).

Neurogenetic Disorders in the Basque Population.

Marti Masso JF, Zarranz JJ, Otaegui D, Lopez de Munain A.

Ann. Hum. Genet. 2015; 79: 57-75. FI: 2.211 (Q3).

Clinical Response to Thalidomide in the Treatment of Intracranial Tuberculomas: Case Report.

de la Riva P, Urtasun M, Castillo-Trivino T, Camino X, Arruti M, Mondragon E, Lopez de Munain A.

Clin. Neuropharmacol. 2013; 36: 70-72. FI: 1.815 (Q3).

A review of travel time estimation and forecasting for Advanced Traveller Information Systems.

Mori U, Mendiburu A, Alvarez M, Lozano JA.

TRANSPORTMETRICA A. 2015; 11: 119-157. FI: 1.333 (Q3).

Review of the novelties presented at the 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (II).

Fernández O, Álvarez-Cermeno JC, Arroyo-González R, Brieva L, Iles-Hernández MC, Casanova-Estruch B, Comabella M, De las Heras V, García-Merino JA, Hernández-Pérez M, Izguierdo G, Meca-Lallana JE, Muñoz-García D, Olascoaga J, Oreja-Guevara C, Prieto JM, Ramio-Torrenta L, Rodríguez-Antigüedad A, Romero-Pinel L, Sánchez F, Tellez N, Tintore M, Montalban X, Post-Ectrims G.

Rev. Neurología. 2012; 54: 734-749. FI: 1.218 (Q3).

Grp Post-ECTRIMS. Review of the novelties presented at the 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I).

Fernández O, Álvarez-Cermeno JC, Arroyo-González R, Brieva L, Calles-Hernández MC, Casanova-Estruch B, Comabella M, De las Heras V, García-Merino JA, Hernández-Pérez MA, Izguierdo Go, Meca-Lallana JE, Muñoz-García D, Olascoaga J, Oreja-Guevara C, Prieto JM, Ramio-Torrenta L, Rodríguez-Antigüedad A, Romero-Pinel L, Sánchez F, Tellez N, Tintore M, Montalban X

Rev. Neurología. 2012; 54: 677-691. FI: 1.218 (Q3).

Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I).

Fernandez O, Arnal-Garcia C, Arroyo-Gonzalez R, Brieva L, Calles-Hernandez MC, Casanova-Estruch B, Comabella M, de las Heras V, Garcia-Merino JA, Hernandez-Perez MA, Izquierdo G, Matas E, Meca-Lallana JE, del Mar Mendibe-Bilbao M, Munoz-Garcia D, Olascoaga J, Oreja-Guevara C, Prieto JM, Ramio-Torrenta L, Rodriguez-Antigueedad A, Saiz A, Tellez N, Villar LM, Tintore M, Grp Post-ECTRIMS.

Rev. Neurologia. 2013; 57: 217-229. FI: 1.179 (Q4).

Grp Post-ECTRIMS. Review of the novelties from the 2014 ECTRIMS-ACTRIMS Joint Congress, presented at the 7th Post-ECTRIMS meeting (I).

Fernandez O, Alvarez-Cermeno JC, Arroyo R, Brieva L, Calles-Hernandez MC, Casanova-Estruch B, Comabella M, Garcia-Merino JA, Ginestal R, Izquierdo G, Meca-Lallana JE, Mendibe-Bilbao MM, Montalban X, Munoz-Garcia D, Olascoaga J, Oliva-Nacarino P, Oreja-Guevara C, Ramio-Torrenta L, Romero-Pinel L, Rodriguez-Antigueedad A, Saiz A, Tintore M.

Rev. Neurologia. 2015; 61: 215-224. FI: 0.830 (Q4).

Spanish consensus on the use of natalizumab (Tysabri (R) – 2011.

Fernández O, García-Merino JA., Arroyo, R., Álvarez-Cermeno JC., Arbizu T, Izquierdo G, Saiz A, Olascoaga J, Rodríguez-Antigüedad A, Prieto JM, Oreja-Guevarak C, Hernández M A, Montalban X.

Neurología. 2012; 27: 432-441. FI: 0.790 (Q4).

Review of the novelties from the 31st ECTRIMS Congress, 2015, presented at the 8th Post-ECTRIMS meeting.

Fernandez O, Rodriguez-Antiguedad A, Olascoaga J, Oreja-Guevara C, Prieto JM, Mendibe-Bilbao MM, Garcia-Merino JA, Ramio-Torrenta L, Ginestal R, Meca-Lallana JE, Romero-Pinel L, Munoz D, Saiz A, Calles-Hernandez MC, Izquierdo G, Villar LM, Oliva-Nacarino P, Arnal-Garcia C, Comabella M, Brieva L, Arroyo R, Montalban X.

Revista De Neurologia. 2016; 62: 559-569. FI: 0,743 (Q4).

Editorials

Published: 0 / 0

Letters

Published: 6 / 6

Ventricular tachycardia on chronic fingolimod treatment for multiple sclerosis.

Castillo-Trivino T, Lopetegui I, Alarcon-Duque JA, Lopez de Munain A, Olascoaga J.

J. Neurol. Neurosurg. Psychiatry. 2015; 86: 931-932. FI: 6.807 (Q1).

TACI mutation in Good’s Syndrome: In search of a genetic basis.

Sáenz-Cuesta M, Martínez-Pomar N, de Gracia J, Echaniz P, Villegas E, Prada A, Otaegui D, Matamoros N, Cuadrado E.

Clin. Immunol. 2012; 145: 27-30. FI: 4.046 (Q2).

An Evaluation of Methods for Estimating the Number of Local Optima in Combinatorial Optimization Problems.

Hernando L, Mendiburu A, Lozano JA.

Evol. Comput. 2013; 21: 625-658. FI: 2.109 (Q1).

Failure mode and effect analysis applied to the procedure for intrathecal chemotherapy.

de la Riva P, Martinez MT, Arruti M, Urtasun MA.

Neurologia. 2015; 30: 62-64. FI: 1.381 (Q4).

Autoimmune hepatitis in a patient with multiple sclerosis under treatment with glatiramer acetate.

Arruti M, Castillo-Triviño T, de la Riva P, Martí-Masso JF, López de Munain A, Olascoaga J

Rev. Neurología. 2012; 55: 190-192. FI: 1.218 (Q3).

Acute retinal necrosis due to herpes simplex virus type 1 within three years after a herpetic encephalitis.

Arruti M, Aldazabal M, Blanco A, Pineiro L, Soledad M, Gonzalez F, Lopez de Munain A.

Rev. Neurologia. 2014; 58: 45-46. FI: 0.926 (Q4).

Others

Published: 4 / 4

Necrosis retiniana aguda por virus herpes simple tipo 1 a los tres años de una encefalitis herpética.

Arruti M, Aldazabal M, Blanco A, Piñeiro L, Zapico MS, González F, López de Munain A.

Rev. Neurologia. 2014; 58: 45-46. FI: 0.926 (Q4).

Javier Urcola Echeverria (1937-2014) In Memoriam.

Olascoaga J.

Rev. Neurologia. 2014; 10: 480. FI: 0.926 (Q4).

Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Navarra, Gipuzkoa y La Rioja.

Ayuso T, Marzo-Sola ME, Castillo-Trivino T, Soriano G, Otano MA, Lopez MA, Croitoru IM, Olascoaga J.

Revista De Neurologia. 2016; 63: -. FI: 0,743 (Q4).

Respuesta al tratamiento con interferon beta en pacientes con esclerosis multiple. Validacion del Rio Score.

Rio J, Rovira A, Blanco Y, Sainz A, Perkal H, Robles R, Ramio-Torrenta L, Diaz RM, Arroyo R, Urbaneja P, Fernandez O, Garcia-Merino JA, Reyes MP, Oreja-Guevara C, Prieto JM, Izquierdo G, Olascoaga J, Alvarez-Cermeno JC, Simon E, Pujal B, Comabella M, Montalban X.

Revista De Neurologia. 2016; 63: 145-150. FI: 0,743 (Q4).

Projects

Projects 8 / 8

Creation of a multi-omic analysis platform to accelerate biomarker discovery. Comic.

Investigador principal: David Otaegui Bichot. Entidad financiadora: POCTEFA-Interreg IV A. Año inicio: 2013. Año final: 2015.

Rol de las micropartículas como biomarcador en Esclerosis Múltiple.

Investigador principal: David Otaegui Bichot. Entidad financiadora: Gobierno Vasco, Departamento de Salud. Año inicio: 2012. Año final: 2015.

Papel de las vesículas extracelulares como promotoras de la remielinización en la Esclerosis Múltiple.

Investigador principal: David Otaegui Bichot. Entidad financiadora: Gobierno Vasco, Departamento de Salud. Año inicio: 2014. Año final: 2017.

Marcadores biológicos de respuesta y predicción en el tratamiento de la Esclerosis Múltiple con Natalizumab y Fingolimod. Predem.

Investigador principal: David Otaegui Bichot. Entidad financiadora: Gobierno Vasco, Departamento de Desarrollo Económico y Competitividad. Año inicio: 2013. Año final: 2014.

T Cell Channelosomics in Multiple Sclerosis. Mschannelomics.

Investigador principal: David Otaegui Bichot. Entidad financiadora: POCTEFA-Interreg IV A. Año inicio: 2013. Año final: 2015.

Optimización de la cadena de frío en el ámbito hospitalario.

Investigador principal: David Otaegui. Entidad financiadora: Hospital Universitario Donostia. Año inicio: 2014. Año final: 2015.

Biomarcadores de Esclerosis Múltiple en LCR y suero.

Investigador principal: Álvaro Prada Iñurrategui. Entidad financiadora: Gobierno Vasco, Departamento de Salud. Año inicio: 2012. Año final: 2015.

Efecto de la vitamina D en pacientes con Esclerosis Múltiple remitente-recurrente.

Investigador principal: Javier Olascoaga Urtaza. Entidad financiadora: Gobierno Vasco, Departamento de Salud. Año inicio: 2012. Año final: 2015.