Basic-Clinical Research in Neurology

The research group was born out of the clinical research which has been conducted in HUCA’s Neurology Department since it was established, on the basis of the extensive case history of all types of neurological diseases diagnosed in the department. This clinical research was progressively developed and systematised into specific areas of neurology, while collaborations with several basic researchers were established, of which the collaboration with the genetics division is particularly noteworthy.
The group’s work is highly translational and its lines of research are focused on gaining more in-depth knowledge of the physiopathological bases of neurological diseases. This supports the search for new diagnostic markers which can enable earlier diagnosis and improved characterisation of neurological pathologies – these generally being complex, with a significant degree of overlap between different diseases – and which can be used as prognostic factors. The group also contributes to the treatment and prevention of neurological diseases: from non-pharmacological interventions (lifestyle, risk-factor control) to new drugs (clinical trials sponsored by third parties or the group itself) and even the search for new therapeutic strategies that have not been described before (technological development projects).
Our work may currently be divided into three lines of research (Neurodegenerative Diseases, Neurological Pathology Biomarkers, and Cerebrovascular Disease). The group has obtained funding from a variety of sources, including several regional and national project grants, international consortia, R&D projects with companies and phase II to phase IV clinical trials.

Neurodegenerative Diseases

• The genetic basis of neurodegenerative diseases (Alzheimer’s and Parkinson’s Disease)
• Neurodegeneration biomarkers (plasma, CSF, neuroimaging)
• Neuropsychology in neurodegenerative pathology
• New therapies for neurodegenerative diseases

Neurological Pathology Biomarkers

• Research on migraines and other headaches
  • Chronic migraine biomarkers
  • Response of patients with chronic migraines to treatment with botulinum toxin
  • The role of endothelial activation in the development of chronic migraines
  • Possible vascular repercussions of migraines
• Multiple Sclerosis Biomarkers
  • Microparticles and exosomes as multiple sclerosis biomarkers
  • Monitoring therapeutic response through blood biomarkers
  • The role of circulating microvesicles in the progression of multiple sclerosis
  • The value of IgM oligoclonal bands in multiple sclerosis diagnosis
  • Development of new sensors for monitoring multiple sclerosis patients.

Cerebrovascular Disease

• Neurovascular disease biomarkers

• Beetz C, Koch N, Khundadze M, Zimmer G, Nietzsche S, Hertel N, Huebner AK,Mumtaz R, Schweizer M, Dirren E, Karle KN, Irintchev A, Alvarez V, Redies C,Westermann M, Kurth I, Deufel T, Kessels MM, Qualmann B, Hübner CA. A spastic paraplegia mouse model reveals REEP1-dependent ER shaping. J Clin Invest. 2014;124(6):2809.
• Martin G, Asensi V, Montes AH, Collazos J, Alvarez V, Carton JA, Taboada F,Valle-Garay E. Role of plasma matrix-metalloproteases (MMPs) and theirpolymorphisms (SNPs) in sepsis development and outcome in ICU patients. Sci Rep. 2014 May 16;4:5002.
• Cardo LF, Coto E, de Mena L, Ribacoba R, Mata IF, Menéndez M, Moris G, AlvarezV. lpha-synuclein transcript isoforms in three different brain regions fromParkinson’s disease and ealthy subjects in relation to the SNCA rs356165/rs11931074 polymorphisms. Neurosci Lett. 2014 562:45-9.
• Ruiz A, Dols-Icardo O, Bullido MJ, Pastor P, Rodríguez-Rodríguez E, López deMunain A, de Pancorbo MM, Pérez-Tur J, Alvarez V, Antonell A, López-Arrieta J,Hernández I, Tárraga L, Boada M, Lleó A, Blesa R, Frank-García A, Sastre I,Razquin C, Ortega-Cubero S, Lorenzo E, Sánchez-Juan P, Combarros O, Moreno F,Gorostidi A, Elcoroaristizabal X, Baquero M, Coto E, Sánchez-Valle R, Clarimón J;dementia genetic Spanish consortium (DEGESCO). Assessing the role of the TREM2p.R47H variant as a risk factor for Alzheimer’s disease and frontotemporaldementia. Neurobiol Aging. 2014 Feb;35(2):444.
• Cardo LF, Coto E, de Mena L, Ribacoba R, Moris G, Menéndez M, Alvarez V.Profile of microRNAs in the plasma of Parkinson’s disease patients and healthycontrols. J Neurol. 2013 May;260(5):1420-2.
• Varga RE, Schüle R, Fadel H, Valenzuela I, Speziani F, Gonzalez M, Rudenskaia G, Nürnberg G, Thiele H, Altmüller J, Alvarez V, Gamez J, Garbern JY, Nürnberg P, Zuchner S, Beetz C.Do not trust the pedigree: reduced and sex-dependent penetrance at a novel mutation hotspot in ATL1 blurs autosomal dominant inheritance of spastic paraplegia.Hum Mutat. 2013 Jun;34(6):860-3.
• Mata IF, Checkoway H, Hutter CM, Samii A, Roberts JW, Kim HM, Agarwal P,Alvarez V, Ribacoba R, Pastor P, Lorenzo-Betancor O, Infante J, Sierra M,Gómez-Garre P, Mir P, Ritz B, Rhodes SL, Colcher A, Van Deerlin V, Chung KA,Quinn JF, Yearout D, Martinez E, Farin FM, Wan JY, Edwards KL, Zabetian CP.Common variation in the LRRK2 gene is a risk factor for Parkinson’s disease. Mov Disord. 2012 Dec;27(14):1822-5.
• Cernuda-Morollón E, Larrosa D, Ramón C, Vega J, Martínez-Camblor P, Pascual J. Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine. Neurology. 2013 Oct 1;81(14):1191-6.
• Reglero-Real N, Alvarez-Varela A, Cernuda-Morollón E, Feito J, Marcos-Ramiro B, Fernández-Martín L, Gómez-Lechón MJ, Muntané J, Sandoval P, Majano PL, Correas I, Alonso MA, Millán J. Apicobasal polarity controls lymphocyte adhesion to hepatic epithelial cells. Cell Rep. 2014 Sep 25;8(6):1879-93.
• Serrano-Pertierra E, Cernuda-Morollón E, Brdička T, Hoøejši V, López-Larrea C. L-plastin is involved in NKG2D recruitment into lipid rafts and NKG2D-mediated NK cell migration. J Leukoc Biol. 2014 Sep;96(3):437-45.
• Cernuda-Morollón E, Ramón C, Martínez-Camblor P, Serrano-Pertierra E, Larrosa D, Pascual J. OnabotulinumtoxinA decreases interictal CGRP plasma levels in patients with chronic migraine. Pain. 2015 May;156(5):820-4.
• Cernuda-Morollón E, Ramón C, Larrosa D, Alvarez R, Riesco N, Pascual J. Long-term experience with onabotulinumtoxinA in the treatment of chronic migraine: What happens after one year? Cephalalgia. 2015 Sep;35(10):864-8.
• Cernuda-Morollón E, Martínez-Camblor P, Alvarez R, Larrosa D, Ramón C, Pascual J. Increased VIP levels in peripheral blood outside migraine attacks as a potential biomarker of cranial parasympathetic activation in chronic migraine. Cephalalgia. 2015 Apr;35(4):310-6.
• Marcos-Ramiro B, García-Weber D, Barroso S, Feito J, Ortega MC, Cernuda-Morollón E, Reglero-Real N, Fernández-Martín L, Durán MC, Alonso MA, Correas I, Cox S, Ridley AJ, Millán J. RhoB controls endothelial barrier recovery by inhibiting Rac1 trafficking to the cell border. J Cell Biol. 2016 May 9;213(3):385-402.
• Riesco N, Pérez-Alvarez AI, Verano L, García-Cabo C, Martínez-Ramos J, Sánchez-Lozano P, Cernuda-Morollón E, Pascual J. Prevalence of cranial autonomic parasympathetic symptoms in chronic migraine: Usefulness of a new scale. Cephalalgia. 2016 Apr;36(4):346-50.
• Serrano-Pertierra E, Benavente L, Blanco-gelaz MA, Fernández-Martín JL, Lahoz CH, Calleja S, López- Larrea C, Cernuda-Morollón E. Lysphosphatidylcholine induces vascular somooth muscle cell membrane vesiculation: potential role in atherosclerosis through caveolin-1 regulation. Proteomics and Bioinformatics 2014; 7(10): 332-339.
• Ramón C, Cernuda-Morollón E, Pascual J. Calcitonin gene-related peptide in peripheral blood as a biomarker for migraine. Curr Opin Neurol. 2017 Jun;30(3):281-286.
• Tell-Marti G, Puig-Butille JA, Gimenez-Xavier P, Segu-Roig A, Potrony ,Badenas C, Alvarez V, Millán JM, Trujillo-Tiebas MJ, Ramos-Arroyo MA, Milà M,Puig S. The p. R151C Polymorphism in MC1R Gene Modifies the Age of Onset in Spanish Huntington’s Disease Patients. Mol Neurobiol. 2017 Jul;54(5):3906-3910.
• Bustamante A, López-Cancio E,Pich S, Penalba A, Giralt D, García-Berrocoso T, Ferrer-Costa C, Gasull T, Hernández-Pérez M, Millan M, Rubiera M, Cardona P, Cano L, Quesada H, Terceño M, Silva Y, Castellanos M, Garces M, Reverté S, Ustrell X, Marés R, Baiges JJ, Serena J, Rubio F, Salas E, Dávalos A, Montaner J. Blood Biomarkers for the Early Diagnosis of Stroke: The Stroke-Chip Study. Stroke. 2017 Sep;48(9):2419-2425.
• De Meyer SF, Andersson T, Baxter B, Bendszus M, Brouwer P, Brinjikji W, Campbell BC, Costalat V, Dávalos A, Demchuk A, Dippel D, Fiehler J, Fischer U, Gilvarry M, Gounis MJ, Gralla J, Jansen O, Jovin T, Kallmes D, Khatri P, Lees KR, López-Cancio E, Majoie C, Marquering H, Narata AP, Nogueira R, Ringleb P, Siddiqui A, Szikora I, Vale D, vonKummer R, Yoo AJ, Hacke W, Liebeskind DS; Clot Summit Group. Analyses of thrombi in acute ischemic stroke: A consensus statement on current knowledge and future directions. Int J Stroke. 2017 Aug;12(6):606-614.
• Dávalos A, Cobo E, Molina CA, Chamorro A, de Miquel MA, Román LS, Serena J, López-Cancio E, Ribó M, Millán M, Urra X, Cardona P, Tomasello A, Castaño C, Blasco J, Aja L, Rubiera M, Gomis M, Renú A, Lara B, Martí-Fàbregas J, Jankowitz B, Cerdà N, Jovin TG; REVASCAT Trial Investigators. Safety and efficacy of thrombectomy in acute ischaemic stroke (REVASCAT): 1-year follow-up of a randomised open-label trial. Lancet Neurol. 2017 May;16(5):369-376.
• Abilleira S, Ribera A, Cardona P, Rubiera M, López-Cancio E, Amaro S, Rodríguez-Campello A, Camps-Renom P, Cánovas D, de Miquel MA, Tomasello A, Remollo S, López-Rueda A, Vivas E, Perendreu J, Gallofré M; Catalan Stroke Code and Reperfusion Consortium. Outcomes After Direct Thrombectomy or Combined Intravenous and Endovascular Treatment Are Not Different. Stroke. 2017 Feb;48(2):375-378.
• López-Cancio E, Ricciardi AC, Sobrino T, Cortés J, de la Ossa NP, Millán M, Hernández-Pérez M, Gomis M, Dorado L, Muñoz-Narbona L, Campos F, Arenillas JF, Dávalos A. ReportedPrestrokePhysicalActivityIsAssociatedwith Vascular EndothelialGrowth Factor Expression and Good Outcomes after Stroke. J Stroke Cerebrovasc Dis. 2017 Feb;26(2):425-430.
• López-Cancio E, Jovin TG, Cobo E, Cerdá N, Jiménez M, Gomis M, Hernández-Pérez M, Cáceres C, Cardona P, Lara B, Renú A, Llull L, Boned S, Muchada M, Dávalos A. Endovascular treatmentimprovescognition after stroke: A secondaryanalysisof REVASCAT trial. Neurology. 2017 Jan 17;88(3):245-251.

Prospective, Non-intervention Study of Patients with Mild to Moderate Alzheimer’s Disease and their Carers in Four European Countries

• Principal Investigator: Marta Blázquez Estrada
• Participating Investigator: Manuel Menéndez González
• Duration: 20/02/2017 to 20/02/2018
• Funding Body: Merck-Sharp and Dhome Corp
• Reference Number: MER-ALZ-2016-01

Progress Study: Post Market Clinical Follow Up Evaluating the Infinity Deep Brain Stimulation Implantable Pulse Generator System

• Principal Investigator: Marta Blázquez Estrada
• Participating Investigators: Esther Suárez San Martín and Ciara García Fernández
• Duration: 06/11/2017 to 06/11/2018
• Funding Body: SJM International INC
• Reference Number: CRD_784/SMJ-CIP-10061

European Multicentre Retrospective Prospective Cohort Study to Observe Safinamide Safety Profile and Pattern of Use in Clinical Practice During the First Commercialization Phase

• Principal Investigator: Marta Blázquez Estrada
• Participating Investigators: Esther Suárez San Martín and Ciara García Fernández
• Duration: May 2017 to December 2020
• Funding Body: Zambon
• Reference Number: Z7219N02

Programme for Detecting Oligoclonal Bands in CSF as a Diagnostic Support Tool for Multiple Sclerosis Patients

• Principal Investigator: Pedro Oliva Nacarino
• Duration: 13/05/2015 to 31/12/2015
• Funding Body: MERCK
• Reference Number: FUO-EM-17315

An Open-Label Study To Evaluate The Efficacy And Safety Of Ocrelizumab In Patients With Relapsing Remitting Multiple Sclerosis Who Have A Suboptimal Response To And Adequate Course Of Disease-Modifying Treatment

• Principal Investigator: Pedro Oliva Nacarino
• Participating Investigators: Antonio Saiz Ayala, Elena Santamarta Liébana and Jorge Peña Suárez
• Duration: 04/05/2016 to 31/12/2018
• Funding Body: Roche Farma
• Reference Number: MA30005

A Prospective, Multicentre, Observational Post-authorisation Safety Study to Evaluate the Long Term Safety Profile of Lemtrada® (Alemtuzumab) Treatment in Patients with Relapsing Forms of Multiple Sclerosis

• Principal Investigator: Pedro Oliva Nacarino
• Duration: 2016 to 2021
• Funding Body: Sanofi Aventis
• Reference Number: OBS13434

Anti-Alpha-4 Integrin Antibodies in the Treatment of Multiple Sclerosis

• Principal Investigators: Pedro Oliva Nacarino and Eva Cernuda Morollón
• Duration: 2013 to 2015
• Funding Body: BiogenIDEC

Laboratory Techniques to Support the Diagnosis, Classification, Prognosis and Monitoring of Therapeutic Response in Multiple Sclerosis Patients

• Principal Investigator: Pedro Oliva Nacarino
• Participating Investigator: Eva Cernuda Morollón
• Duration: 2014 to 2015
• Funding Body: Sanofi Aventis

A Phase 2, Double-Blind, Randomised, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of ANAVEX2-73 for Cognitive Impairment in Patients with Parkinson’s Disease with Dementia

• Principal Investigator: Marta Blázquez Estrada
• Participating Investigator: Manuel Menéndez González
• Duration: 2018
• Reference Number: ANAVEX-2-73-001

• Two ISPA groups participate in developing a new treatment for Alzheimer’s (17/11/2018)