Neurodegenerative Diseases

Group leader: Javier Ruiz Martínez, Ph.D.

Donostialdea IHO javier.ruizmartinez@osakidetza.eus

Strategic Objectives

Neurodegenerative diseases are one of the main sources of incapacity in the population over 60 years old with considerable repercussions on health system costs. The aim of this line of work is to find out more about the causal factors and physiopathology of these diseases as well as studying possible therapeutic agents that help control symptoms or delay their evolution. This involves carrying out translational research that includes both clinical and basic studies (animal models, in vitro studies, genetic, proteomics, etc.) with a multi-disciplinary focus involving studies of post-mortem cerebral and histological imagery in patients and animal models, molecular studies, genetic studies, etc.

The main aims are:

  • Clinical, neuropsychological, genetic and proteomic characterisation of these diseases.
  • Search for diagnostic and/or evolutionary bio-markers.
  • Developing cellular and animal models.
  • Obtaining neural progenitors by means of reprogramming.
  • Studying the human physiopathology and animal models of different clinical aspects of neurodegenerative diseases.

Main lines of research

  • Parkinson’s disease.
      • Studies on genetic forms of the disease and family members carrying mutations.
              • Studies of biomarkers in patients and asymptomatic carriers of LRRK2 gene mutations.
              • Identification of new genetic forms in families.
              • Natural history of genetic Parkinson’s disease.
      • Cognitive and behavioural studies (dementia / cognitive deterioration and Impulse Control Disorder).
            • Physiopathological characterisation of Impulse Control Disorder.
            • Clinical study on Impulse Control Disorder incidence and risk factors in Spain.
            • Multi-centre clinical study in Spain on treatment for Impulse Control Disorder.
            • Study of early bio-markers for cognitive deterioration associated with Parkinson’s Disease.
      • Physiopathological characterisation of dyskinesia and impulsive disorder in animal models.
      • Histopathological study of bowel dysfunction in patients and family members with Parkinson’s disease.
  • Essential tremors.
      • Search for endophenotypes and genomic and cerebral imagery study.
  • Frontotemporal dementia and other dementias.
    • Clinical and molecular characterisation of alterations to the progranulin gene and other associated genes.
    • Other molecular alterations in frontotemporal dementias.
  • Neuropsychiatric diseases: psychosis and depression.
    • Psychosis: studies of family ties and/or association with diagnosis of schizophrenia or bipolar disorder.
    • Depression: neuroinflammatory markers in depression and its treatment.
      • Translational project aiming to take a clinical problem to a lab assessment. This aims to investigate by measuring proinflammatory and anti-inflammatory factors and neuro-glial injury in periphery blood in patients with depression.
    • First psychotic episodes.
      • Awareness of illness in first psychotic episodes. Explanatory models and predictive value in the therapeutic response.
      • Consumption of nicotine in patients with recently initiated schizophrenia. An explanatory model from the hypothesis of self-medication and assessment of its incidence on the progress of the disease.
    • Cognitive functions.
      • Impact of combined treatment (PegInterferon-alpha (PegInterferon-alpha Ribavirin) on cognitive functions of patients with Chronic Hepatitis due to the Hepatitis C virus.
    • Metabolomics applied to detecting biomarkers in schizophrenia.

Team Members

Name Surname
Center E-mail
Marta Alonso Pinedo Donostialdea IHO
Silvia Arostegui Uranga Donostialdea IHO silvia.arosteguiuranga@osakidetza.eus
Myriam Barandiarán Amillano Donostialdea IHO miriamjesus.barandiaranamillano@osakidetza.eus
Alberto Bergareche Yarza Donostialdea IHO alberto.bergarecheyarza@osakidetza.eus
César Caballero Gaudes BCBL c.caballero@bcbl.eu
Manuel Francisco Carreriras Valiña BCBL manuelfrancisco.carreiras@ehu.eus
María de Arriba Sanchez Donostialdea IHO maria.dearribasanchez@osakidetza.eus
Jon Andoni Duñabeitia Landáburu BCBL j.dunabeitia@bcbl.eu
Esther Fernandez Pardavila OSATEK efernandez@osatek.net
Ana Gorostidi Pagola Biodonostia HRI ana.gorostidi@biodonostia.org
Maria Begoña Indakoetxea Juanbeltz Donostialdea IHO begona.indacoecheajuanbeltz@osakidetza.eus
Elisabet Mondragón Rezola Donostialdea IHO elisabet.mondragonrezola@osakidetza.eus
Fermín Moreno Izco Donostialdea IHO
Amaia Oregi Viteri Biodonostia HRI amaya.oregui@biodonostia.org
Pedro Manuel Paz Alonso BCBL kepa.pazalonso@bcbl.eu
Mª Cruz Rodriguez Oroz
Imanol Querejeta Ayerdi Donostialdea IHO imanol.querejetaayerdi@osakidetza.net
Ana Vinagre Aragón Donostialdea IHO ana.vinagre@biodonostia.org
Saioa Yurrita Montesinos Donostialdea IHO saioa.yurritamontesinos@osakidetza.eus

Scientific Output

Originals

Published: 10 / 207

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2).

Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, Bannon F, Ahn JV, Johnson CJ, Bonaventure A, Marcos-Gragera R, Stiller C, Azevedo G, Chen WQ, Ogunbiyi OJ, Rachet B, Soeberg MJ, You H, Matsuda T, Bielska-Lasota M, Storm H, Tucker TC, Coleman MP, CONCORD Working Grp.

Lancet. 2015; 385: 977-1010. FI: 45.217 (Q1).

The expanding universe of disorders of the basal ganglia.

Obeso JA, Rodriguez-Oroz MC, Stamelou M, Bhatia KP, Burn DJ.

Lancet. 2014; 384: 523-531. FI: 39.207 (Q1).

Prolonged-release oxycodone-naloxone for treatment of severe pain in patients with Parkinson’s disease (PANDA): a double-blind, randomised, placebo-controlled trial.

Trenkwalder C, Chaudhuri KR, Martinez-Martin P, Rascol O, Ehret R, Vališ M, Sátori M, Krygowska-Wajs A, Marti MJ, Reimer K, Oksche A, Lomax M, DeCesare J, Hopp M, PANDA study group.

Lancet Neurol. 2015; 14: 1161-1170. FI: 21.896 (Q1).

Correlating Metal Poisoning with Zeolite Deactivation in an Individual Catalyst Particle by Chemical and Phase-Sensitive X-ray Microscopy.

Ruiz-Martinez J, Beale AM, Deka U, O'Brien MG, Quinn PD, Mosselmans JFW, Weckhuysen BM.

Angew. Chem. Int. Edit. 2013; 52: 5983-5987. FI: 13.734 (Q1).

Neuropathologic substrates of Parkinson disease dementia.

Irwin DJ, White MT, Toledo JB, Xie SX, Robinson JL, Van Deerlin V, Lee VMY, Leverenz JB, Montine TJ, Duda JE, Hurtig HI, Trojanowski JQ.

Ann. Neurol. 2012; 72: 587-598. FI: 11.089 (Q1).

Grey matter hypometabolism and atrophy in Parkinson’s disease with cognitive impairment: a two-step process.

Gonzalez-Redondo R, Garcia-Garcia D, Clavero P, Gasca-Salas C, Garcia-Eulate R, Zubieta JL, Arbizu J, Obeso JA, Rodriguez-Oroz MC.

Brain. 2014; 137: 2356-2367. FI: 10.226 (Q1).

The caudate: a key node in the neuronal network imbalance of insomnia?

Stoffers D, Altena E, van der Werf YD, Sanz-Arigita EJ, Voorn TA, Astill RG, Strijers RLM, De Van Someren Eus JW.

Brain. 2014; 137: 610-620. FI: 10.226 (Q1).

The subthalamic nucleus and inhibitory control: impact of subthalamotomy in Parkinson’s disease.

Obeso I, Wilkinson L, Casabona E, Speekenbrink M, Luisa Bringas M, Alvarez M, Alvarez L, Pavon N, Rodriguez-Oroz MC, Macias R, Obeso JA, Jahanshahi M.

Brain. 2014; 137: 1470-1480. FI: 10.226 (Q1).

Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson’s disease.

Bastide MF, Meissner WG, Picconi B, Fasano S, Fernagut PO, Feyder M, Francardo V, Alcacer C, Ding Y, Brambilla R, Fisone G, Jon Stoessl A, Bourdenx M, Engeln M, Navailles S, De Deurwaerdère P, Ko WK, Simola N, Morelli M, Groc L, Rodriguez MC, Gurevich EV, Quik M, Morari M, Mellone M, Gardoni F, Tronci E, Guehl D, Tison F, Crossman AR, Kang UJ, Steece-Collier K, Fox S, Carta M, Angela Cenci M, Bézard E.

PROG NEUROBIOL. 2015; 132: 96-168. FI: 9.992 (Q1).

Universal brain signature of proficient reading: Evidence from four contrasting languages.

Rueckl JG, Paz-Alonso PM, Molfese PJ, Kuo WJ, Bick A, Frost SJ, Hancock R, Wu DH, Mencl WE, Duñabeitia JA, Lee JR, Oliver M, Zevin JD, Hoeft F, Carreiras M, Tzeng OJ, Pugh KR, Frost R.

Proc Natl Acad Sci U S A. 2015; 112: 15510-15515. FI: 9.674 (Q1).

Reviews

Published: 10 / 10

Dyskinesias and impulse control disorders in Parkinson’s disease: From pathogenesis to potential therapeutic approaches.

Jimenez-Urbieta H, Gago B, de la Riva P, Delgado-Alvarado M, Marin C, Rodriguez-Oroz MC.

Neurosci. Biobehav. Rev. 2015; 56: 294-314. FI: 8.802 (Q1).

Second language syntactic processing revealed through event-related potentials: An empirical review.

Caffarra S, Molinaro N, Davidson D, Carreiras M.

Neurosci. Biobehav. Rev. 2015; 51: 31-47. FI: 8.802 (Q1).

Management of Impulse Control Disorders in Parkinson’s Disease: Controversies and Future Approaches.

Samuel M, Rodriguez-Oroz M, Antonini A, Brotchie JM, Chaudhuri K, Brown RG, Galpern WR, Nirenberg MJ, Okun MS, Lang, Anthony E.

Mov. Disord. 2015; 30: 150-159. FI: 5.680 (Q1).

Muscle wasting in myotonic dystrophies: a model of premature aging.

Mateos-Aierdi A, Goicoechea A, Aiastui A, Fernandez-Torron R, Garcia-Puga M, Matheu A, Lopez de Munain A.

Aging Neurosci. 2015. FI: 4.000 (Q1).

Oxidative stress and Parkinson’s disease.

Blesa J, Trigo-Damas I, Quiroga-Varela A, Jackson-Lewis VR.

Front. Neuroanat. 2015; 9: 91-0. FI: 3.544 (Q1).

The Relationship Between Atrophy and Hypometabolism: Is It Regionally Dependent in Dementias?.

Rodriguez-Oroz MC, Gago B, Clavero P, Delgado-Alvarado M, Garcia-Garcia D, Jimenez-Urbieta H.

Curr. Neurol. Neurosci. Rep. 2015; 15. FI: 3.059 (Q2).

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).

Rasagiline in monotherapy in patients with early stages of Parkinson’s disease and in combined and adjunct therapy to levodopa with moderate and advanced stages.

Pagonabarraga J, Rodriguez-Oroz MC.

Rev. Neurologia. 2013; 56: 25-34. FI: 1.179 (Q4).

Parkinson’s Disease Mild Cognitive Impairment: Application and Validation of the Criteria.

Geurtsen GJ, Hoogland J, Goldman JG, Schmand BA, Troester AI, Burn DJ, Litvan I, MDS Study Grp Validation PD-MCI Cr.

J. Parkinsons Dis. 2014; 4: 131-137. FI: 1.097 (Q4).

Editorials

Published: 4 / 4

Methylphenidate for freezing of gait in Parkinon’s disease.

Rodríguez-Oroz MC.

Lancet Neurol. 2012; 11: 569-570. FI: 23.462 (Q1).

The MAPK1/3 pathway is essential for the deregulation of autophagy observed in G2019S LRRK2 mutant fibroblasts.

Bravo-San Pedro JM., Gómez-Sánchez R, Niso-Santano M, Pizarro-Estrella E, Aiastui-Pujana A, Gorostidi A, Climent V, López de Maturana R, Sánchez-Pernaute R, López de Munain A, Fuentes JM, González-Polo RA.

Autophagy. 2012; 8: 1537-1539. FI: 7.453 (Q1).

On the left anterior negativity (LAN): The case of morphosyntactic agreement: A Reply to Tanner et al.

Molinaro N, Barber HA, Caffarra S, Carreiras M.

Cortex. 2015; 66: 156-159. FI: 5.128 (Q1).

Pathological Crying After Subthalamic Nucleus Stimulation Commentary.

Rodriguez-Oroz MC, Obeso JA.

Mov. Disord. 2013; 28: 1349-1350. FI: 4.558 (Q1).

Letters

Published: 10 / 11

Erosion of universal health coverage in Spain.

Legido-Quigley H, Urdaneta E, Gonzalez A, La Parra D, Muntaner C, Alvarez-Dardet C, Martin-Moreno JM, McKee M.

Lancet. 2013; 382: 1977. FI: 39.060 (Q1).

Analysis of the CHCHD10 gene in patients with frontotemporal dementia and amyotrophic lateral sclerosis from Spain.

Dols-Icardo O, Nebot I, Gorostidi A, Ortega-Cubero S, Hernandez I, Rojas-Garcia R, Garcia-Redondo A, Povedano M, Llado A, Alvarez V, Sanchez-Juan P, Pardo J, Jerico I, Vazquez-Costa J, Sevilla T, Cardona F, Indakoechea B, Moreno F, Fernandez-Torron R, Munoz-Llahuna L, Moreno-Grau S, Rosende-Roca M, Vela A, Munoz-Blanco JL, Combarros O, Coto E, Alcolea D, Fortea J, Lleo A, Sanchez-Valle R, Esteban-Perez J, Ruiz A, Pastor P, Lopez De Munain A, Perez-Tur J, Clarimon J, Dementia Genetics Spanish Consorti.

Brain. 2015; 138: 400-24. FI: 9.196 (Q1).

Michael J. Fox Foundation LRRK2 Consortium: geographical differences in returning genetic research data to study participants.

Alcalay RN, Aasly J, Berg D, Bressman S, Brice A, Brockmann K, Chan P, Clark L, Cormier F, Corvol JC, Durr A, Facheris M, Farrer M, Foroud TM, Gasser T, Giladi N, Halter C, Lang A, Langston JW, Marras C, Marti-Masso JF, Ruiz Martinez J, Mejia-Santana H, Mirelman A, Pont-Sunyer C, Orr-Urtreger A, Raymond D, Saunders-Pullman R, Schüle B, Tanner C, Tolosa E, Urkowitz A, Vilas D, Wise A, Marder K.

Genet Med. 2014; 16: 644-645. FI: 6.435 (Q1).

Screening for POLG W748S and A467T mutations in ataxia patients from Spain.

Pelayo-Negro AL, Sánchez-Quintana C, Rodríguez-Oroz MC, Volpini V, Zeviani M, Tola-Arribas MA, Berciano J, Infante J.

Mov. Disord. 2012; 27: 1326-1327. FI: 4.505 (Q1).

From ileostomy to sudden quadriplegia with electrocardiographic abnormalities: a short and unfortunate path.

Delgado M, Palacio E, Pelayo AL, Lerena P, Berciano J.

Neurol. Sci. 2013; 34: 1471-1473. FI: 1.412 (Q3).

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).

Progressive gait disorder and epilepsy secondary to venous stroke due to dural arteriovenous fistula type III.

Navalpotro-Gomez I, Rodriguez-Campello A, Vivanco-Hidalgo RM, Vivas E, Roquer-Gonzalez J.

Neurologia. 2015; 30: 450-451. FI: 1.381 (Q4).

Current neurological mortality rates in infectious endocarditis.

De la Riva P, de Arce Borda AM, Diez N, Goenaga MA.

Neurologia. 2014; 29: 312-313. FI: 1.289 (Q4).

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

Arruti M, Castillo-Trivino T, de la Riva P, Martí-Massó JF, López de Munain A, Olascoaga J.

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

Acute cerebellitis following Epstein-Barr virus infection in two young women.

de la Riva P, Martinez MT, Arruti M, Diez N, Mondragon E, Gonzalo N, Tainta M, Marti-Masso JF.

Rev. Neurologia. 2013; 56: 252-253. FI: 1.179 (Q4).

Others

Published: 5 / 5

Oftalmoplejía completa unilateral sin pérdida de visión como forma de presentación de una apoplejía pituitaria.

Delgado-Alvarado M, Riancho J, Riancho-Zarrabeitia L, Sedano MJ, Polo JM, Berciano J.

Rev Clin Esp. 2013; 213: e67-70. FI: 2.008 (Q2).

Javier Urcola Echeverria (1937-2014) in memoriam.

Marti-Masso JF.

Neurología. 2015. FI: 1.381 (Q4).

Rombencefalitis y endocarditis por Listeria monocytogenes: una asociacion no descrita.

Tainta M, de la Riva P, Gonzalez F, Marti-Masso JF, Goenaga MA.

Revista De Neurologia. 2016; 63: 46-48. FI: 0,743 (Q4).

Rhomboencephalitis and endocarditis caused by Listeria monocytogenes: an unreported association.

Tainta M, de la Riva P, Gonzalez F, Marti-Masso JF, Goenaga MA.

Revista De Neurologia. 2016; 63: 46-48. FI: 0,743 (Q4).

Advances in gene therapies for limb-girdle muscular dystrophies.

Mateos A, Aiastui A, Goicoechea M, López de Munáin A.

Advances in Regenerative Biology. 2014. FI: 0.000 (Q0).

Projects

Projects 12 / 12

Estimulación del núcleo subtalámico en el trastorno de control de impulsos en la enfermedad de Parkinson.

Investigador principal: María Cruz Rodríguez Oroz. Entidad financiadora: Gobierno de España, Ministerio de Ciencia e Innovación. Año inicio: 2012. Año final: 2015.

Gabapentina en el trastorno de control de impulsos de la enfermedad de Parkinson: Estudio multicéntrico, doble ciego, aleatorizado, controlado con placebo.

Investigador principal: María Cruz Rodríguez Oroz. Entidad financiadora: Gobierno de España, Ministerio de Sanidad, Servicios Sociales e Igualdad. Año inicio: 2012. Año final: 2015.

Trastorno de impulsividad en la enfermedad de Parkinson: Fisiopatología e impacto lingüístico.

Investigador principal: María Cruz Rodríguez Oroz. Entidad financiadora: Diputación Foral de Gipuzkoa. Año inicio: 2014. Año final: 2015.

Deterioro cognitivo en la enfermedad de Parkinson: Correlato histológico del hipometabolismo y la atrofia cerebral en un modelo animal y efecto de la estimulación cognitiva en pacientes.

Investigador principal: María Cruz Rodríguez Oroz. Entidad financiadora: ISCIII Instituto de Salud Carlos III. Año inicio: 2014. Año final: 2017.

Multimodal MRI in Basque LRRK2 PD. Multipagen.

Investigador principal: María Cruz Rodríguez Oroz. Entidad financiadora: POCTEFA-Interreg IV A. Año inicio: 2013. Año final: 2015.

Mecanismos fisiopatológicos del trastorno del control de impulsos en la enfermedad de Parkinson. Estudio en pacientes y desarrollo de un modelo animal.

Investigador principal: María Cruz Rodríguez Oroz. Entidad financiadora: ISCIII Instituto de Salud Carlos III. Año inicio: 2012. Año final: 2015.

Estudio de biomarcadores en la fase temprana de la demencia en la enfermedad de Parkinson.

Investigador principal: María Cruz Rodríguez Oroz. Entidad financiadora: Gobierno Vasco, Departamento de Salud. Año inicio: 2012. Año final: 2015.

Potencial de las células precursoras derivadas de piel en el tratamiento de la enfermedad de Alzheimer.

Investigador principal: José Julio Rodríguez Arellano. Entidad financiadora: Gobierno Vasco, Departamento de Salud. Año inicio: 2012. Año final: 2015.

Cuantificación de productos de PCR.

Investigador principal: Ana Gorostidi Pagola. Entidad financiadora: Diputación Foral de Gipuzkoa. Año inicio: 2014. Año final: 2015.

Heterodimeros de receptores dopaminérgicos: Papel en el desarrollo de Diskinesias en la enfermedad de Parkinson. Herteda.

Investigador principal: Belén Gago Calderón. Entidad financiadora: Gobierno Vasco, Departamento de Desarrollo Económico y Competitividad. Año inicio: 2013. Año final: 2014.

Conciencia de enfermedad en primeros episodios psicóticos. Modelos explicativos y valor predictivo en la respuesta terapéutica.

Investigador principal: Imanol Querejeta Ayerdi. Entidad financiadora: Gobierno Vasco, Departamento de Salud. Año inicio: 2012. Año final: 2015.

Caracterización clínica de los endofenotipos del temblor esencial familiar y esporádico.

Investigador principal: José Félix Martí Massó. Entidad financiadora: ISCIII Instituto de Salud Carlos III. Año inicio: 2011. Año final: 2014.