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Hospital de Sant Pau

Hospital de Sant Pau

El Hospital de la Santa Creu i Sant Pau es un centro de alta complejidad que, con seis siglos de existencia, representa la institución hospitalaria decana del estado español. Con la entrada del siglo XXI, el Hospital de la Santa Creu i Sant Pau inició un importante proceso que culminó en el que es hoy su tercer emplazamiento desde su nacimiento hace más de 600 años. El nuevo Hospital se empezó a construir en el año 2.000 en la parte norte del recinto de Sant Pau, en la esquina de las calles Mas Casanovas y Sant Quintí, para dar respuesta a las nuevas necesidades sanitarias. Este edificio está formado por un bloque principal que acoge básicamente la actividad ambulatoria (36.022 m2) del que se despliegan, como dedos, cuatro bloques de hospitalización (46.878 m2). http://www.santpau.cat

Entrevista con el Dr. Jordi Surrallés

Fuente: Excodra | Publicado: 22-01-2018
La Genética es clave en la medicina del futuro: preventiva, personalizada y participativa. En pocos años vamos a ser capaces de diagnosticar las más de 5000 enfermedades genéticas actuales, muchas de ellas raras. La genética servirá no sólo para confirmar el diagnóstico sino, en muchos casos, para establecer hipótesis diagnósticas en pacientes sin diagnostico clínico determinante.
Derechos: Equipo asistencial del Servicio de Genética del Hospital de Sant Pau..
10 comentarios

Jordi, para comenzar, ¿en qué consiste la terapia génica, cómo se lleva a término?

Hay miles de enfermedades genéticas causadas por mutaciones en algún gen lo que hace que las células no puedan hacer su función. La terapia génica consiste en recuperar la función defectuosa a través de introducción de copias sanas en las células del paciente, normalmente usando un virus modificado que llamamos vector viral.

¿Qué características tiene y cuál es la relevancia de la anemia de Fanconi como modelo de enfermedad para el avance en el desarrollo de las terapias génicas contra el cáncer?

La anemia de Fanconi es una enfermedad genética rara caracterizada por fallo medular que produce anemia y otras alteraciones hematológicas, malformaciones congénitas y predisposición al cáncer. Los genes implicados en anemia de Fanconi son genes reparadores de mutaciones y, en ausencia de reparación, la acumulación de mutaciones incrementa el riesgo de que aparezca una combinación determinada de mutaciones que transforme las células sanas en tumorales.



Las enfermedades hereditarias que son potencialmente tratables por trasplante de progenitores hematopoyéticos, como la anemia de Fanconi, la hemofilia o la talasemia, es donde más avances se han logrado en terapia génica: se extraen las células madre hematopoyéticas del paciente como si fuera un donante de trasplante, se corrige el defecto genético introduciendo el gen sano con vector lentiviral, y se vuelven a inyectar las células sanas al individuo para que aniden, se expandan en número y curen la enfermedad.


No cabe duda que la anemia de Fanconi es punta de lanza en el desarrollo de estas terapias innovadoras.

Las mutaciones genéticas son una de las bases de la evolución, pero también de desarrollo de síndromes y enfermedades… se hacen muy significativas en las denominadas enfermedades raras, como en la mencionada anemia de Fanconi, ¿cuál es el proceso de estudio de estas mutaciones, desde sus consecuencias en el individuo a su caracterización genética?

Si hablamos del estudio de mutaciones en genes ya conocidos, hay un amplio abanico de técnicas para la detección de mutaciones patogénicas que puedan explicar o llevar a un diagnóstico. Esto se puede hacer de forma prenatal o postnatal.



En los últimos años, la secuenciación masiva de grandes cantidades de DNA a costes asumibles, ha provocado una revolución en el campo de las aplicaciones de la genética a la medicina.


En algunos casos nos encontramos ante enfermedades no diagnosticadas para las que aun no se sabe cual es el gen causante. En estos casos la técnica más usada actualmente para descubrir nuevos genes implicados en enfermedades raras es la secuenciación de exomas enteros, es decir, la secuenciación de la parte más informativa de todos los genes. Gracias a esta tecnología mi grupo ha descubierto la base genética de varias enfermedades lo que facilitará no sólo un mejor diagnóstico sino también un mejor entendimiento de la enfermedad, base imprescindible para el desarrollo de nuevas terapias

Una de vuestras líneas de investigación está destinada a los mecanismos de la inestabilidad genómica y predisposición al cáncer. Pregunto desde el desconocimiento, ¿es muy elevada la incidencia de cánceres debidos a fallos en la maquinaria molecular de reparación del ADN? ¿Qué acercamientos estáis proponiendo y realizando para usar estos genes implicados en reparación como dianas terapéuticas?

Mutaciones en genes reparadores explican entre un 5% y un 10% de los cánceres más comunes, como el de mama o el de colon. Dado que la mayor parte de la quimioterapia actúa hipermutando el DNA de las células tumorales, los mecanismos de reparación actúan como un mecanismo de defensa del tumor. Por este motivo son una muy buena diana terapéutica y hay muchos grupos de investigación y empresas farmacéuticas buscando inhibidores de la reparación del DNA. Un buen ejemplo son los inhibidores de la PARP, unas drogas que son muy efectivas en tumores con mutaciones en genes implicados en la reparación como BRCA1 o BRCA2.

Genéricamente, en la lucha contra el cáncer se abren varios frentes, desde prevención con hábitos de vida saludables, a nuevas herramientas y conocimientos para el diagnóstico precoz, a diferentes tratamientos una vez que se ha desarrollado, ¿cuánto están aportando los estudios genéticos para prevención, diagnóstico y tratamiento?



Los estudios genéticos son la base de la medicina personalizada. Actualmente ya se hacen estudios genéticos rutinarios en los hospitales para elegir el mejor tratamiento antitumoral en función de las características genéticas del tumor y del paciente.


En los últimos años, la genética ha permitido estudiar DNA tumoral circulante en la sangre de los pacientes, la llamada biopsia líquida. Esta semana se ha publicado en la prestigiosa revista Science que con un simple ensayo genético en DNA tumoral circulante es posible detectar la presencia de tumores en fase pre-sintomática. Sin duda estos avances permitirán un diagnóstico muy precoz del tumor en fase pre-metastásica

Recientemente habéis publicado dos artículos en Genetics in medicine, sobre mutaciones en el gen FANCM y la vía (FA)/BRCA de reparación de ADN. Esta vía tiene múltiples implicaciones, en la anemia de Fanconi, así en fragilidad cromosómica como relacionada con toxicidad a quimioterapia, menopausia prematura y en predisposición al cáncer. Ya lo hemos ido comentando, pero más en concreto, ¿cuáles son los elementos que hacen que esta vía tenga tantas ramificaciones fenotípicas, tan diferentes efectos sobre el organismo cuando hay mutaciones en ella?

La ruta Fanconi/BRCA está implicada en la reparación de enlaces cruzados entre las dos cadenas del DNA. Este tipo de mutación es muy tóxica para las células sanas y sobretodo las tumorales que se dividen mucho y, no en vano, el cisplatino, una de las quimioterapias mas usada, actúa sobre el DNA de este modo. Por tanto, esta ruta de reparación no sólo es importante porque cuando falla causa varias enfermedades humanas de predisposición al cáncer sino también porque es una muy buena diana terapéutica para muchos tipos tumorales en población general.    

Saliéndonos un poco de lo anterior, este año has sido nombrado Director del Servicio de Genética del Hospital Sant Pau de Barcelona, queremos felicitarte por ello, ¿qué retos tenéis por delante?

Aunque sigo como Catedrático de Genética de la UAB, en 2017 tomé el cargo de Director del Servicio de Genética del Hospital de Sant Pau, hospital universitario de la UAB. Mi principal función para estos próximos años es potenciar la medicina genómica en el hospital a partir de la innovación tecnológica basada en secuenciación masiva y la investigación transnacional de excelencia. El plan estratégico del Servicio de Genética es innovar para hacernos más porosos en el hospital.  Durante el año 2017 hemos incorporado un nuevo secuenciador masivo de alta capacidad así como un nuevo Adjunto con perfil Bioinformático para poder trabajar en esta dirección. El nuevo edificio del instituto de investigación será sin duda un gran estímulo en esta dirección estratégica. El Hospital de Sant Pau, como hospital terciario universitario tiene una triple misión asistencial, investigadora y docente en su plan estratégico: potenciar la medicina de alta complejidad, contribuir a la generación de nuevo conocimiento, y transmitirlo a las nuevas generaciones de estudiantes. 

Jordi, para terminar, un poco relacionado con lo anterior pero a nivel general, pensando en el futuro, ¿cómo imaginas el futuro próximo de la medicina, de la clínica, con todos los aportes que están llegando desde la genética, tanto en terapia, como en edición de genomas, secuenciaciones masivas y demás aportes a nivel de conocimientos de nuestra genética y su manipulación?

¡Para contestar a esta pregunta necesitaría varias páginas!



La Genética es clave en la medicina del futuro: preventiva, personalizada y participativa. En pocos años vamos a ser capaces de diagnosticar las más de 5000 enfermedades genéticas actuales, muchas de ellas raras.


La genética servirá no sólo para confirmar el diagnóstico sino, en muchos casos, para establecer hipótesis diagnósticas en pacientes sin diagnostico clínico determinante, para determinar el pronóstico o los riegos del paciente a partir de los cuales estableces medidas preventivas y profilácticas, elegir el mejor medicamento en cada caso, y para detectar de forma temprana tumores y hacerles un seguimiento clínico. Finalmente, la genética se ira implantando también de forma pre-concepcional, de forma que estudiando genéticamente a los padres se podrá prevenir el nacimiento de nuevos enfermos.


Enlace a página del hospital: http://www.santpau.cat/es/web/public/equip-directiu/-/journal_content/56/125011/378443
Comentarios:
 
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shenyuhang20180420
20-04-2018 03:04

Dr. Jordi Surrallés

Dr. Jordi Surrallés

With a PhD in Genetics and postdoctoral experience in The Netherlands (Leiden University Medical Center) and Finland (Finnish Institute of Occupational Health), he set up his research team at the UAB where he is currently Full Professor of Genetics and, since January 2017, he was appointed Director of the Genetics Service at Sant Pau Hospital, Barcelona. He is Director of the Biobank of DNA Repair Syndromes, Head of the UAB Chromosome Fragility Laboratory Service and team leader at the Center for Biomedical Network Research on Rare Diseases (CIBERER). Dr. Surrallés has supervised over 25 research grants awarded from public and private institutions world-wide and participated in clinical trials, several patents and contracts with private foundations and biotech-pharma companies. He has given tens of invited lectures in international meetings. He has published over 100 articles and book chapters including articles in Nature, Blood, Am J Hum Genet, Genes and Dev, PNAS, and supervised 25 PhD and Master students. He is reviewer of tens of scientific journals including Science, Nature, Molecular Cell Biology and Blood and Referee of national and international funding agencies including European Research Council (ERC), Agence Nationale de la Recherche-ANR (France), Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR), ANEP (Ministerio de Ciencia y Tecnología), Cancer Research UK (UK), Commission of the European Union, Member of Selection Board Subcomitte on Genetic Diseases and Cancer ISCIII (Spanish Ministry of Science and Innovation), Duch Cancer Society (The Netherlands), Fanconi Anemia Research Fund Inc. (USA), FIS (Ministerio de Sanidad y Consumo), German-Israeli Fundation for Scientic Research and Development (Germany), INSERM (France), and the French National Cancer Institute (France). His research interests are cancer-prone rare genetic syndromes with defective DNA repair with special focus in Fanconi anemia. He also investigates the genetics of familiar cancer syndromes and performs therapeutic research including gene and cell therapy approaches and cell-based drug screening platforms. A long term goal is to understand the mechanisms that maintain genome stability and protect us from disease, cancer, and ageing and to translate this knowledge to develop novel therapeutic and diagnostic strategies.

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