Charcot-Marie-Tooth disease (CMT) is the most frequent hereditary neuropathy, with a prevalence in Cantabria of 28 cases per 100,000 inhabitants (Combarros et al, Acta Neurol Scand 1987; 75: 9-12). Under the acronym CMT2 are included the axonal forms with autosomal dominant inheritance. The IDIVAL Neurodegenerative Diseases Group, based on the Neurology Service of the Hospital Universitario Marqués de Valdecilla, in 1986, described the clinical, neurophysiological and neuropathological study of an extensive Cantabrian strain that allowed the definition of the phenotype as a sensory-motor lumbosacral neuronopathy with Distance-dependent axonal degeneration (dying-back phenomenon) (Berciano et al, Brain 1986; 109: 897-914). Clinically it is manifested by foot cavus, and syndrome of peroneal muscular atrophy of varying degree.
Almost two decades later, in collaboration with the Neurogenetic Group of the University of Antwerp (Belgium) and through linkage analysis, the locus of the disease was located at cr12q12-q13.3 (Nelis et al, J Med Genet 2004; : 193-7), entering OMIM under catalog number 608591. In the following years the localization was refined, and the study of candidate genes (Peeters K, Doctoral thesis, Antwerp University, Belgium, 2014) was unsuccessful.
In the last five years, the aforementioned group has carried out a clinical re-evaluation on the available members of the third and fourth generation. Dr. Antonio García (Clinical Neurophysiology Service of the University Hospital Marqués de Valdecilla) repeated electrophysiological studies protocolized according to the requirements of the CMTNS scale (Shy et al, Neurology 2005; 64: 1209-1214); And Dr. Elena Gallardo (Radiological Diagnostic Service of the University Hospital Marqués de Valdecilla) underwent MRI examination of the leg muscles, with the protocol she had introduced in the CMT1A study with duplication (Gallardo et al, Brain 2006; 129 : 426-37). At this point, it was established that in CMT2G there is incomplete penetrance, a very rare phenomenon in any other CMT syndrome, which greatly complicates any linkage study. In any case, muscular MRI has been an excellent biomarker, detecting an evident and constant fat atrophy of the intrinsic musculature of the feet and to a lesser extent of the muscles of the posterior superficial compartment of the legs. Together with the clinical, neurophysiological and muscular MRI we were able to discriminate affected subjects, potential carriers of a subclinical pathogenic mutation (incomplete penetrance), and subjects at risk but healthy.
With a better phenotypic definition, the next step was to retake the genetic linkage analysis and then go on a “hunt” for a pathogenic mutation. The new locus was redefined in the cr9q31.3-q34.2 region. Using high throughput sequencing techniques, a novel pathogen mutation was identified in LRSAM1, p.Cyst694Tyr, which codes for the enzyme ligase of the ubiquitin E3 protein. Other punctate mutations of this gene have been associated with CMT2P. In patient lymphoblasts, the mutation did not influence the levels of LRSAM1 or those of its ubiquitinated target TSG101. The mutation is associated, however, with several transcriptional modifications including up-regulation of other ligases, NEDD4L and TNFRSF21 (Peeters et al, Ann Neurol 2016 Sep 30. doi: 10.1002 / ana.24775. [Epub ahead of Print]; PMID: 27686364).
Our work concludes that CMT2G is caused by a misconception of LRSAM1, so it should be reclassified as CMT2P. MRI of the leg muscles can be used to detect minimal signs of the disease. Transcriptomic analysis in the cells of several patients has allowed the identification of new factors associated with LRSAM1 dysfunction, which offer new therapeutic targets shared with amyotrophic lateral sclerosis and Alzheimer's disease.
Reference: Peeters K, Palaima P, Pelayo-Negro AL, García A, Gallardo E, García-Barredo R, Mateiu L, Baets J, Menten B, De Vriendt E, De Jonghe P, Timmerman V, Infante J, Berciano J, Jordanova A. Charcot-Marie-Tooth disease type 2G redefined by a novel mutation in LRSAM1. Ann Neurol. 2016 Sep 30. doi: 10.1002/ana.24775.
Charcot-Marie-Tooth disease (CMT) is the most frequent hereditary neuropathy, with a prevalence in Cantabria of 28 cases per 100,000 inhabitants (Combarros et al, Acta Neurol Scand 1987; 75: 9-12). Under the acronym CMT2 are included the axonal forms with autosomal dominant inheritance. The IDIVAL Neurodegenerative Diseases Group, based on the Neurology Service of the Hospital […]
As of today, the provisional resolution of those admitted and excluded from the call for predoctoral contracts IDIVAL-UC 2016 is published.
The list of admitted excluded can be consulted in the following link.
The subsanation period is open until October 28. Consultations can be made on the matter at 942-201059.
As of today, the provisional resolution of those admitted and excluded from the call for predoctoral contracts IDIVAL-UC 2016 is published. The list of admitted excluded can be consulted in the following link. The subsanation period is open until October 28. Consultations can be made on the matter at 942-201059. More information
A novelty in Horizon 2020 is the Pilot on Open Research Data which aims to improve and maximise access to and re-use of research data generated by projects. Projects funded under topics NMBP-23 to NMBP-29 inclusive, on modelling and nanotechnology safety, will by default participate in the Pilot on Open Research Data in Horizon 2020.
Projects have the possibility to opt out of the Pilot, provided a justification is given for doing so. Participation in the Pilot is not taken into account during the evaluation procedure. Proposals will not be evaluated favourably because they are part of the Pilot and will not be penalised for opting out of the Pilot. More information can be found under General Annex L of the work programme.
A further new element in Horizon 2020 is the use of Data Management Plans (DMPs), detailing what data the project will generate, whether and how it will be exploited or made accessible for verification and re-use, and how it will be curated and preserved. The use of a DMP is required for projects participating in the Open Research Data Pilot. Other projects are invited to submit a DMP if relevant for their planned research. Only funded projects are required to submit a DMP. Further guidance on the Pilot on Open Research Data and Data Management is available on the Participant Portal.
IDIVAL contact support: Paloma González Álvarez <innovacion4@idival.org>; Lorena Agüero <proyectos1@idival.org>
A novelty in Horizon 2020 is the Pilot on Open Research Data which aims to improve and maximise access to and re-use of research data generated by projects. Projects funded under topics NMBP-23 to NMBP-29 inclusive, on modelling and nanotechnology safety, will by default participate in the Pilot on Open Research Data in Horizon 2020. […]
The third conference of the program Santander Biomedical Lectures organized by IDIVAL, the University of Cantabria and the IBBTEC will be imparted by Jesús San Miguel next November 17 with the title “Multiple Myeloma of Biology to Therapeutics”.
Jesús San Miguel, Director of Clinical and Translational Medicine at the University of Navarra, will focus on:Briefly summarizing his trajectory, Prof. Jesús San Miguel studied medicine at the University of Navarra and took his doctorate in Salamanca. Prior to his current position, for 22 years, he has been Professor of Medicine at the University of Salamanca and Head of the Hematology Service at the University Hospital; he has also been Researcher at the Cancer Research Center of Salamanca and Scientific Director of the Institute of Biomedical Research of Salamanca (IBSAL). He is currently President of the International Myeloma Society.
The third conference of the program Santander Biomedical Lectures organized by IDIVAL, the University of Cantabria and the IBBTEC will be imparted by Jesús San Miguel next November 17 with the title “Multiple Myeloma of Biology to Therapeutics”. Jesús San Miguel, Director of Clinical and Translational Medicine at the University of Navarra, will focus on: […]
The journal Nature Neuroscience has just published an article on a study, in which researchers from the Psychiatry group of the University of Cantabria-IDIVAL-CIBERSAM, led by Benedicto Crespo-Facorro, head of the IDIVAL Group of Psychiatry, Have identified five new sites in the genome, and replicated two previously described sites associated with intracranial volume.
The study was carried out in a sample of 32,348 adults using a complete genome association (GWAS) analysis in populations of two international research consortia, CHARGE and ENIGMA, among which are Cantabrian researchers.
“We have focused on studying the genetic basis for determining the size of the brain in the early stages of development,” explains Crespo-Facorro, “and it really does seem that brain volume determines cognitive development in childhood And protection against cognitive degenerative diseases in adulthood. “
“It is a topic of debate at international level and that leads us to place this research in one of the lines of maximum interest as it is to know what is the relationship between brain volume and cognitive function or predisposition to have neurodegenerative diseases in the age Adult, “adds the researcher.
And indeed, as explained in the article, “there seems to be a significant genetic correlation both with the circumference of the cranial circumference and with cognitive functioning in infancy and adulthood. And, therefore, the size of the brain that is reached during development can be a marker that can determine cognitive functioning in childhood as in adult life, in relation to cognitive reserve brain. “
Discussion about the influence of brain size
The differences in brain size between people are determined by genetic variants and also by the influence of environmental factors. There is a broad historical debate about whether the size of the brain has a direct impact on the intellectual capacity of the person.
The knowledge of how genetic variants can determine these differences in size opens new lines of research in the knowledge of the biological determinants of brain development and, therefore, of neuropsychiatric disorders.
According to the head of the research group in Psychiatry, “these genes described give us a new perspective on biological processes that determine how the volume of brain that is reached during development varies between individuals.”
Thus, the cognitive reserve hypothesis states that brain size may be an element that modifies individual predisposition to suffer from age-related brain diseases.
“Although not conclusively, these findings support the idea that variations in normal brain size may be important for the intellectual development of individuals and for predisposition to neurodegenerative diseases.”
Together with Crespo-Facorro, Head of Section of the Psychiatry Service of the University of Cantabria, Professor of Psychiatry of the UC and member of the Royal Medicine Academy of Cantabria, the researcher Roberto Roz Santiáñez and Diana Tordesillas, Responsible for the Neuroimaging Unit of IDIVAL.
The result is part of those obtained by the international consortium ENIGMA, in which the only Spanish representation is the Institute of Sanitary Research (IDIVAL) and the Center for Biomedical Research in Network in the Area of Mental Health (CIBERSAM).
The ENIGMA consortium, created in 2009 by Drs. Paul Thompson and Nick Martin, comprises more than 300 scientists from 185 institutions and 33 countries sharing their resources to gain a better understanding of the effects of genes on brain structure and function. ENIGMA allows us to study brain, genetic and clinical data from 30,000 patients worldwide.
Reference:
“Novel genetic loci underlying human intracranial volume identified through genome-wide association”
http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.4398.html
Adams HH, et al.
Nat Neurosci. 2016 Oct 3. doi: 10.1038/nn.4398.
The journal Nature Neuroscience has just published an article on a study, in which researchers from the Psychiatry group of the University of Cantabria-IDIVAL-CIBERSAM, led by Benedicto Crespo-Facorro, head of the IDIVAL Group of Psychiatry, Have identified five new sites in the genome, and replicated two previously described sites associated with intracranial volume. The study […]
La Consejería de Sanidad del gobierno de Cantabria aprueba el modelo de contrato de Ensayos Clínicos para el sistema Sanitario Público de Cantabria a través de una orden publicada en el Boletín Oficial de Cantabria el día 7 de Octubre.
Esta orden considera a IDIVAL con ente gestor de todos los contratos de Ensayos Clínicos a los que aplica este modelo y desarrolla un modelo de reparto económico con la siguiente distribución:
a) Costes indirectos del ensayo: 30% del coste total del ensayo.
b) Compensación para el fomento de la actividad investigadora: 35% (como mínimo) del coste total del ensayo.
c) Compensación al equipo investigador: un 35% (como máximo) del coste total del ensayo. Los investigadores principales y colaboradores son las personas que figuran en el protocolo del ensayo clínico.
La compensación para el fomento de la actividad investigadora en el grupo/servicio investigador será depositada por la entidad gestora de I+D+i en la cuenta de investigación correspondiente para ser reinvertida en las actividades de I+D+i del investigador o del equipo investigador de acuerdo con las normas internas de funcionamiento de IDIVAL.
La compensación al equipo investigador será gestionada por la entidad gestora de I+D+i de acuerdo con sus normas internas de funcionamiento de IDIVAL y según las indicaciones del investigador principal, de conformidad con lo establecido en la disposición adicional décima de la Ley de Cantabria 9/2010, de 23 de diciembre, de personal estatutario de instituciones sanitarias de la Comunidad Autónoma de Cantabria, en conexión con la disposición adicional tercera de la Ley de Cantabria 10/2012 de medidas Fiscales y Administrativas.
El nuevo contrato está vigente desde su publicación en el BOC y supone un claro avance para la facilitación de la gestión de ensayos clínicos, en aras de su transparencia, de acuerdo con las normas actuales de la industria farmacéutica y de los principios de gestión de la I+D+i en el sector público.
Para más información al respecto, contactar con Blanca del Pozo (email: eclinicos3@idival.org)
Link a la Agencia de Ensayos Clínicos IDIVAL
La Consejería de Sanidad del gobierno de Cantabria aprueba el modelo de contrato de Ensayos Clínicos para el sistema Sanitario Público de Cantabria a través de una orden publicada en el Boletín Oficial de Cantabria el día 7 de Octubre. Esta orden considera a IDIVAL con ente gestor de todos los contratos de Ensayos Clínicos […]
La Fundación Merck Salud convoca la XXVI edición de las Ayudas Merck de Investigación, dirigidas a promover la investigación biológica y biomédica en España, mediante la financiación de proyectos inéditos. En esta convocatoria, las ayudas se centran en las siguientes áreas de Investigación:
– Investigación Clínica en Alergología
– Investigación Clínica en Cáncer de Cabeza y Cuello
– Investigación Clínica en Cáncer Colorrectal
– Investigación Clínica en Cáncer de Pulmón
– Investigación Clínica en Enfermedades Raras
– Investigación Clínica en Esclerosis Múltiple
– Investigación Clínica en Fertilidad
Se otorgará un total de 7 Ayudas, una por cada área de Investigación de las indicadas en el apartado anterior. Cada una de ellas estará dotada con 30.000€
El plazo límite para la recepción de los proyectos finaliza el 31 de octubre de 2016.
Puedes consultar las bases de esta convocatoria clicando AQUILa Fundación Merck Salud convoca la XXVI edición de las Ayudas Merck de Investigación, dirigidas a promover la investigación biológica y biomédica en España, mediante la financiación de proyectos inéditos. En esta convocatoria, las ayudas se centran en las siguientes áreas de Investigación: – Investigación Clínica en Alergología – Investigación Clínica en Cáncer de Cabeza […]
La Fundación MAPFRE convoca la Beca Primitivo de Vega de Investigación con el objeto de facilitar apoyo económico para la realización de un trabajo científico en el área de atención a las personas mayores. El ámbito de la convocatoria es mundial. Los proyectos de investigación que se presenten a esta convocatoria deberán ceñirse a las siguientes áreas:
No se contemplarán proyectos de investigación de estudios farmacológicos, bioquímicos, moleculares, etc., o que estén incluidos dentro de otro proyecto de investigación.
La dotación económica ascenderá a una cantidad global máxima de 15.000 euros.
El plazo de registro finaliza el 20 de octubre de 2016 (inclusive).
Podeis consultar las bases de esta convocatoria clicando AQUI.
La Fundación MAPFRE convoca la Beca Primitivo de Vega de Investigación con el objeto de facilitar apoyo económico para la realización de un trabajo científico en el área de atención a las personas mayores. El ámbito de la convocatoria es mundial. Los proyectos de investigación que se presenten a esta convocatoria deberán ceñirse a las […]
El próximo jueves (6 de octubre) la Sesión General del Hospital Valdecilla en la Sala Téllez-Plasencia estará a cargo del Dr. Peter McDonald, cirujano cardíaco de Sant Vicent´s (Sidney). Se trata del primer cirujano que realizó un trasplante cardíaco con donante en asistolia en 2014. Actualmente solo existen tres centros en el mundo (Sant Vicent's en Sidney y 2 centros británicos) que tienen un programa de trasplantes cardíacos a partir de donantes en asistolia.
La dificultad de este trasplante radica en la preservación cardiaca preextracción. En un futuro próximo, en Valdecilla, realizaremos este tipo de transplantes con la técnica ECMO, como se hace en el Hospital de Papworth (Cambridge), y aquí puede haber conflicto con el resto de órganos (sobre todo con pulmones e hígado; riñones en menor medida), por lo que creemos puede ser un foro muy interesante al que os invitamos a asistir y debatir.
La difusión de la investigación e innovación es uno de los ejes de actividades de IDIVAL, que se refleja en las Sesiones Hospitalarias, formación en técnicas y metodología investigadora.
El próximo jueves (6 de octubre) la Sesión General del Hospital Valdecilla en la Sala Téllez-Plasencia estará a cargo del Dr. Peter McDonald, cirujano cardíaco de Sant Vicent´s (Sidney). Se trata del primer cirujano que realizó un trasplante cardíaco con donante en asistolia en 2014. Actualmente solo existen tres centros en el mundo (Sant Vicent's en Sidney y 2 centros […]
IDIVAL convoca ayudas para intensificación de médicos o enfermeras pertenecientes al Servicio Cántabro de Salud con actividad asistencial.
Esta intensificación está dedicada a la liberación de tiempo asistencial que facilite el desarrollo de proyectos de investigación o innovación asistencial.
Para su solicitud los candidatos deben presentar, a través de la plataforma de ayudas IDIVAL, su curriculum vitae en formato FECYT, una memoria de actividades previstas para el periodo de intensificación, y los informes pertinentes de autorización de los responsables del centro y Servicio/Unidad a la que pertenece el candidato.
La convocatoria esta abierta hasta el día 30 de Octubre de 2016.
IDIVAL convoca ayudas para intensificación de médicos o enfermeras pertenecientes al Servicio Cántabro de Salud con actividad asistencial. Esta intensificación está dedicada a la liberación de tiempo asistencial que facilite el desarrollo de proyectos de investigación o innovación asistencial. Para su solicitud los candidatos deben presentar, a través de la plataforma de ayudas IDIVAL, su […]
