Pathogenesis and Novel Therapies in Multiple Sclerosis
Our work is focused in understanding the causes and mechanisms leading to brain damage in Multiple Sclerosis. In order to achieve this goal we apply the tools of systems biology and brain imaging to dissect the immunological mechanisms leading to brain damage. In doing so, we apply a multidisciplinary approach involving neurologists, ophthalmologists, bioinformaticians, engineers and biologists, that all contribute to the research program.
Our team has a strong translational interest and is highly focused in innovation. As such we work in translating our research into new tools for treating MS. For example we are developing several new neuroprotective therapies for MS and other brain diseases by targeting different pathways such as the polyamine pathway or the neurotrophin pathway.
In the lab we perform the preclinical development of new therapies in collaboration with spin-off companies: Bionure, Mint-Labs and Fractalmed and at the hospital we will perform the clinical development by carrying out clinical trials. We are also developing several new diagnostic tools such as molecular imaging of the retina, new software for quantifying axonal damage or new biomarkers based in gene expression and metabolomics for predicting the course of the disease.
Finally, we aim to translate our discoveries in collaboration with leading centers around the world in the management of patients with MS, developing personalized medicine by applying computational models in combination with molecular, imaging and clinical databases using advanced computational tools. Most of these efforts are conducted in collaboration with the Spanish MS network from the Instituto de Salud Carlos III and within several European grants and international collaborations.
CLINICAL AND NEUROIMAGING POSTDOCTORAL RESEARCHER
Martinez-Lapiscina EH, Arnow S, Wilson JA, Saidha S, Preiningerova JL,Oberwahrenbrock T, Brandt AU, Pablo LE, Guerrieri S, Gonzalez I, Outteryck O, Mueller AK, Albrecht P, Chan W, Lukas S, Balk LJ, Fraser C, Frederiksen JL, Resto J, Frohman T, Cordano C, Zubizarreta I, Andorra M, Sanchez-Dalmau B, Saiz A, Bermel R, Klistorner A, Petzold A, Schippling S, Costello F, Aktas O, Vermersch P, Oreja-Guevara C, Comi G, Leocani L, Garcia-Martin E, Paul F, Havrdova E, Frohman E, Balcer LJ, Green AJ, Calabresi PA, Villoslada P; IMSVISUAL consortium. Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study. Lancet Neurol. 2016 May;15(6):574-84
Abad E, Sepulcre J, Martinez-Lapiscina EH, Zubizarreta I, Garcia-Ojalvo J, Villoslada P. The analysis of semantic networks in multiple sclerosis identifies preferential damage of long-range connectivity. Mult Scler Relat Disord. 2015 Sep;4(5):387-94. doi: 10.1016/j.msard.2015.07.002. Epub 2015 Jul 8. PubMed PMID: 26346784
Errea O, Moreno B, Gonzalez-Franquesa A, Garcia-Roves PM, Villoslada P. The disruption of mitochondrial axonal transport is an early event in neuroinflammation. J Neuroinflammation. 2015 Aug 28;12:152. doi: 10.1186/s12974-015-0375-8. PubMed PMID: 26310930; PubMed Central PMCID: PMC4551771.
Gabilondo I, Martínez-Lapiscina EH, Fraga-Pumar E, Ortiz-Pérez S, Torres-Torres R, Andorra M, Llufriu S, Zubizarreta I, Saiz A, Sanchez-Dalmau B, Villoslada P. Dynamics of retinal injury after acute optic neuritis. Ann Neurol. 2015 Mar;77(3):517-28.
Martínez-Lapiscina EH, Fraga-Pumar E, Gabilondo I, Martínez-Heras E, Torres-Torres R, Ortiz-Pérez S, Llufriu S, Tercero A, Andorra M, Roca MF, Lampert E, Zubizarreta I, Saiz A, Sanchez-Dalmau B, Villoslada P. The multiple sclerosis visual pathway cohort: understanding neurodegeneration in MS. BMC Res Notes. 2014 Dec 15;7:910. doi: 10.1186/1756-0500-7-910. PubMed PMID: 25512202; PubMed Central PMCID: PMC4300678.
Gabilondo I, Martínez-Lapiscina EH, Martínez-Heras E, Fraga-Pumar E, Llufriu S, Ortiz S, Bullich S, Sepulveda M, Falcon C, Berenguer J, Saiz A, Sanchez-Dalmau B, Villoslada P. Trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis. Ann Neurol. 2014 Jan;75(1):98-107
Marro M, Taubes A, Abernathy A, Balint S, Moreno B, Sanchez-Dalmau B, Martínez-Lapiscina EH, Amat-Roldan I, Petrov D, Villoslada P. Dynamic molecular monitoring of retina inflammation by in vivo Raman spectroscopy coupled with multivariate analysis. J Biophotonics. 2013
Ortiz-Pérez S*, Martínez-Lapiscina EH*, Gabilondo I, Fraga-Pumar E, Martínez-Heras E, Saiz A, Sanchez-Dalmau B, Villoslada P. Retinal periphlebitis is associated with multiple sclerosis severity. Neurology. 2013 Sep 3;81(10):877-81. Equally contributors authors
Pertsovskaya I, Abad E, Domedel-Puig N, Garcia-Ojalvo J, Villoslada P. Transient oscillatory dynamics of interferon beta signaling in macrophages. BMC Syst Biol. 2013 Jul 9;7:59. doi: 10.1186/1752-0509-7-59. PubMed PMID: 23837526; PubMed Central PMCID: PMC3711797.
Gabilondo I, Sepúlveda M, Ortiz-Perez S, Fraga-Pumar E, Martínez-Lapiscina EH, Llufriu S, Solá N, Saiz A, Sanchez-Dalmau B, Villoslada P. Retrograde retinal damage after acute optic tract lesion in MS. J Neurol Neurosurg Psychiatry. 2013 Jul;84(7):824-6
Kotelnikova E, Bernardo-Faura M, Silberberg G, Kiani NA, Messinis D, Melas IN, Artigas L, Schwartz E, Mazo I, Masso M, Alexopoulos LG, Mas JM, Olsson T, Tegner J, Martin R, Zamora A, Paul F, Saez-Rodriguez J, Villoslada P. Signaling networks in MS: a systems-based approach to developing new pharmacological therapies. Mult Scler. 2015 Feb;21(2):138-46. doi: 10.1177/1352458514543339. Epub 2014 Aug 11. PubMed PMID: 25112814.
Bermel RA, Villoslada P. Retrograde trans-synaptic degeneration in MS: a missing link? Neurology. 2014 Jun 17;82(24):2152-3. doi: 10.1212/WNL.0000000000000532. Epub 2014 May 16. PubMed PMID: 24838792
Martínez-Lapiscina EH, Fraga-Pumar E, Pastor X, Gómez M, Conesa A, Lozano-Rubí R, Sánchez-Dalmau B, Alonso A, Villoslada P. Is the incidence of optic neuritis rising? Evidence from an epidemiological study in Barcelona (Spain), 2008-2012. J Neurol. 2014 Apr;261(4):759-67. doi: 10.1007/s00415-014-7266-2. Epub 2014 Feb 16. PubMed PMID: 24532201.
Martínez-Lapiscina EH, Ortiz-Pérez S, Fraga-Pumar E, Martínez-Heras E, Gabilondo I, Llufriu S, Bullich S, Figueras M, Saiz A, Sánchez-Dalmau B, Villoslada P. Colour vision impairment is associated with disease severity in multiple sclerosis. Mult Scler. 2014 Jan 7;20(9):1207-1216. [Epub ahead of print] PubMed PMID: 24399824
New therapies for MS and NMO
- Antigen specific tolerization
- Dendritic cell tolerization
- Nanoparticle tolerization
- Neuroprotective drugs
- Trophic factor mimetics: BN201
Systems biology, precision medicine and big data (Electronic Medical records) in MS
We aim to analyze structural and functional connectivity networks in patients with MS in order to improve our understanding about the organization of brain networks using MS lesions as a perturbation to the networks. In addition, we aim to use the analysis of brain connectivity as biomarkers of the disease.
Combims: A novel drug discovery method based on systems biology: combination therapy and biomarkers for Multiple Sclerosis
CombiMS aims to develop a computational method that will help to discover new combinations of drugs for Multiple Sclerosis (a classic complex disease) based on medical and scientific knowledge, and using computer simulations.
The Sys4MS consortium aims to develop new tools based on systems medicine to improve and personalize the management of patients with a complex disease, Multiple Sclerosis (MS). This requires developing mathematical models into which clinical information and ‘omics data from diverse sources can be integrated, and which can be used to generate algorithms that can predict the disease course and future disability in specific subgroups of MS patients, as well as aiding the selection of the best therapy for each individual.
Web: more info about Sys4MS
- Immunopathogenesis of Paraneoplastic Neurologic Syndrome
- Pathogenesis of Immune-mediated Neurological Disorders
- Pathogenesis and Novel Therapies in Multiple Sclerosis
- Biomarkers and Neuroimaging in Multiple Sclerosis and Neuromyelitis Optica
- Neuroimmunologic Response to Surgical Aggression and Anesthesia
- Visual Pathway Laboratory
- Clinical Muticentric Prospective Studies