{"id":83878,"date":"2021-04-30T09:42:32","date_gmt":"2021-04-30T07:42:32","guid":{"rendered":"https:\/\/ibecbarcelona.eu\/?p=83878"},"modified":"2021-05-06T12:06:20","modified_gmt":"2021-05-06T10:06:20","slug":"hacia-un-tratamiento-para-la-distrofia-miotonica-primer-modelo-3d-con-celulas-de-pacientes","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/es\/hacia-un-tratamiento-para-la-distrofia-miotonica-primer-modelo-3d-con-celulas-de-pacientes\/","title":{"rendered":"Hacia un tratamiento para la distrofia miot\u00f3nica: primer modelo 3D con c\u00e9lulas de pacientes"},"content":{"rendered":"
\"\"
Investigadores del IBEC Juanma Fern\u00e1ndez, Javier Ram\u00f3n y Xiomara Fern\u00e1ndez<\/figcaption><\/figure>\n

La distrofia miot\u00f3nica es una enfermedad<\/span> neuromuscular <\/span>degenerativa hereditaria<\/span> que <\/span>se manifiesta<\/span> principalmente en adulto<\/span>s, afectando a unas 50.000 personas e<\/span>n Espa\u00f1a<\/span>. Lo<\/span>s<\/span> s\u00edntomas var\u00edan desde dificultad para caminar hasta graves problemas neurol\u00f3gicos<\/span>, y conduce<\/span>n<\/span> a una incapacitaci\u00f3n progresiva que <\/span>por desgracia <\/span>lleva a la silla de ruedas a muchos de los afectados.<\/span> Esta enfermedad es muy heterog\u00e9nea<\/span> entre pacientes<\/span> (<\/span>edad de inicio, progresi\u00f3n, <\/span>t<\/span>ransmisi\u00f3n hereditaria<\/span>, <\/span>m\u00fasculos afectados<\/span>)<\/span> lo que hace especialmente complejo el desarrollo de tratamientos gen\u00e9ricos.\u00a0<\/span>\u00a0<\/span><\/p>\n

Actualmente, los f\u00e1rmacos contra la distrofia miot\u00f3nica se desarrollan en modelos animales como <\/span>la <\/span>Drosoph<\/span><\/i>i<\/span><\/i>la<\/span><\/i>, la mosca del vinagre, o en cultivos celulares en 2D<\/span>. <\/span>M\u00e1s tarde <\/span>se prueban en ratones y<\/span>,<\/span> finalmente<\/span> en<\/span> pacientes. Utilizando estos enfoques se han desarrollado algunos f\u00e1rmacos que <\/span>desafortunadamente <\/span>no han podido llegar a las \u00faltimas fases de ensayos cl\u00ednicos porque no eran efectivos en pacientes, poniendo de <\/span>manifiesto la dificultad de extrapolar resultados obtenidos con animales a<\/span> seres<\/span> humanos.<\/span>\u00a0<\/span><\/p>\n

Ahora, el equipo liderado por el <\/span>Profesor de Investigador ICREA y jefe del grupo <\/span>Biosensores para Bioingenier\u00eda<\/span><\/a> en el IBEC, Javier Ram\u00f3n, y<\/span> por el investigador postdoctoral de su equipo Juan<\/span> M. <\/span>Fern\u00e1ndez,<\/span> ha <\/span>desarrollado por primera vez un modelo tridimensional para la distrofia miot\u00f3nica, utilizando t\u00e9cnicas de bioingenier\u00eda y c\u00e9lulas de paciente<\/strong>. El trabajo<\/span>,<\/span> que forma parte de la <\/span>t<\/span>esis doctoral de la investigadora Xiomara Fern\u00e1ndez<\/span> del IBEC, se ha realizado <\/span>en colaboraci\u00f3n con investigadores del instituto de investigaci\u00f3n sanitaria INCLIVA de Valencia<\/span> y se ha<\/span> publicado recientemente en la revista <\/span>Biofabrication<\/span><\/a>,<\/span> abre las puertas a encontrar tratamientos personalizados y efectivos contra esta enfermedad rara y hasta la fecha sin cura.<\/span> Este trabajo se ha financiado en parte con fondos de una <\/span>campa\u00f1a de recaudaci\u00f3n de fondos<\/span><\/a> l<\/span>anzada por<\/span> el IBEC<\/span> desde finales de 2017 hasta finales del 2019.<\/span>\u00a0<\/span><\/p>\n

El nuevo modelo 3D para la distrofia miot\u00f3nica\u00a0<\/strong><\/h2>\n

\"\"<\/span><\/p>\n

Los investigadores han partido de fibroblastos de <\/span><\/span>la piel de <\/span><\/span>un paciente<\/span><\/span>, <\/span><\/span>c\u00e9lulas del tejido conectivo <\/span><\/span>encargado de mantener <\/span><\/span>su <\/span><\/span>estructura<\/span><\/span>,<\/span><\/span> y <\/span><\/span>fueron<\/span><\/span> previamente<\/span><\/span> \u201creprogramado<\/span><\/span>s<\/span><\/span>\u201d para que se convirtiesen en <\/span><\/span>mioblastos<\/span><\/span>, <\/span><\/span>c\u00e9lulas <\/span><\/span>precursoras del m\u00fasculo<\/span><\/span>. Estos mioblastos<\/span><\/span> s<\/span><\/span>e pusieron dentro de un<\/span><\/span>a matriz<\/span><\/span> de <\/span><\/span>gelatina y celulosa<\/span><\/span> y la <\/span><\/span>mezcla se someti\u00f3 a una especie de sello de goma para darle una forma de rect\u00e1ngulos alargados, simulando las fibras musculares<\/span><\/span>. Posteriormente <\/span><\/span>la matriz<\/span><\/span> se incub\u00f3 bajo las condiciones idea<\/span><\/span>l<\/span><\/span>es para que los mioblastos siguiesen su desarrollo<\/span><\/span>.<\/span>\u00a0<\/span><\/p>\n

 <\/p>\n

Imagen<\/span><\/span><\/strong>:<\/span><\/span> Imagen de microscop\u00eda <\/span><\/span>confocal<\/span><\/span> de <\/span><\/span>m\u00fasculo <\/span><\/span>in vitro<\/span><\/span> desarrollado a partir de c\u00e9lulas de paciente<\/span><\/span> en que se aprecia la <\/span><\/span>tridimensionalidad del tejido. En azul se marcan los n\u00facleos<\/span><\/span> celulares<\/span><\/span> y en rojo <\/span><\/span>el <\/span><\/span>m\u00fasculo esquel\u00e9tico.<\/span><\/span><\/span><\/h6>\n
\n

Lo que observamos es que, <\/span><\/span>a diferencia de los cultivos celulares cl\u00e1sicos,<\/span><\/span> l<\/span><\/span>as c\u00e9lulas <\/span><\/span>de paciente <\/span><\/span>en nuestro modelo <\/span><\/span>son<\/span><\/span> capaces de fusionarse forma<\/span><\/span>ndo<\/span><\/span> fibras musculares<\/span><\/span> que adoptan<\/span><\/span> la forma 3D <\/span><\/span>encontrada <\/span><\/span>en los m\u00fasculos y esencial para su funcionamiento<\/span><\/span><\/span><\/span>. <\/strong>
\n\u00a0<\/strong><\/p>\n

Juan M. Fernandez <\/strong>
\n<\/span><\/p>\n<\/blockquote>\n

Posibilidad de probar f\u00e1rmacos de forma personalizada y r\u00e1pida\u00a0<\/strong><\/h2>\n

Para evaluar la funcionalidad del nuevo modelo 3D, <\/span>los investigadores <\/span>han aplicado<\/span> a las fibras musculares<\/span> un f\u00e1rmaco<\/span>, <\/span>AntagomiR-23b<\/span>,<\/span> previamente desarrollado <\/span>por algunos <\/span>autores <\/span>de este trabajo, y que en <\/span>un futuro no muy lejano<\/span> entrar\u00e1 en fase de ensayos cl\u00ednicos<\/span> a trav\u00e9s de la empresa <\/span>Arthex<\/span> Biotech<\/span><\/a> que <\/span>continua el <\/span>progreso<\/span> de la terapia. Observaron <\/span>que tanto las caracter\u00edsticas moleculares como estructurales de las fibras derivadas del paciente<\/span> recuperaron sus par\u00e1metros normales<\/span> al ser tratadas<\/span>, validando <\/span>su utilizaci\u00f3n<\/span> para el desarrollo de nuevos f\u00e1rmacos.\u00a0<\/span>\u00a0<\/span><\/p>\n

Adem\u00e1s, <\/span>este <\/span>mode<\/span>lo <\/span>tiene un coste reducido<\/span>, <\/span>su implementaci\u00f3n es simple<\/span> y puede acelerar el proceso de desarrollo de nuevos tratamientos, ya que es m\u00e1s r\u00e1pido <\/span>comparado con el uso de <\/span>animales. <\/span>R<\/span>epresenta <\/span>un<\/span> gran paso <\/span>hacia la medicina personalizada<\/span>, <\/span>ya que t<\/span>ener en cuenta la <\/span>enorme<\/span> variabilidad entre pacientes es clave en el momento de buscar tratamientos<\/span> para esta enfermedad.<\/span>\u00a0<\/span><\/p>\n

Este nuevo modelo<\/span><\/span> permitir\u00e1 probar diferentes <\/span><\/span>f\u00e1rmacos<\/span><\/span> y administrar al paciente el que ha dado mejor resultado con sus propias c\u00e9lulas. De esta manera el tratamiento ser\u00e1 <\/span><\/span>personalizado, <\/span><\/span>m\u00e1s efectivo y adem\u00e1s se prescinde del uso de animales<\/span><\/span>.\u00a0<\/strong>
\n\u00a0<\/strong><\/p>\n

Xiomara Fernandez\u00a0<\/strong>
\n<\/span><\/p>\n<\/blockquote>\n

La distrofia miot\u00f3nica\u00a0<\/strong><\/h2>\n

La enfermedad est\u00e1 causada por una mutaci\u00f3n en el gen <\/span><\/span>DMPK<\/span><\/span> (<\/span><\/span>Dystrophia<\/span><\/span> Myotonica<\/span><\/span> Protein<\/span><\/span> Kinase<\/span><\/span>) que causa el \u201csecuestro\u201d de prote\u00ednas esenciales para el correcto funcionamiento de los m\u00fasculos, en especial la<\/span><\/span>s<\/span><\/span> prote\u00edna<\/span><\/span>s<\/span><\/span> \u201c<\/span><\/span>M<\/span><\/span>uscleblind<\/span><\/span>\u201d. Al <\/span><\/span>reducirse su <\/span><\/span>disponibilidad no puede realizar normalmente sus funciones, entre ellas hacer la transici\u00f3n de otras prote\u00ednas de una fase fetal o infantil a una fase adulta. La consecuencia es que los pacientes tienen prote\u00ednas que no funcionan como las de un adulto. Dos ejemplos son el receptor de insulina, que en pacientes de distrofia miot\u00f3nica no funciona correctamente y causa diabetes, y la prote\u00edna que regula la entrada y salida de cloro de las c\u00e9lulas musculares, los conocidos como canales de cloro. Su mal funcionamiento es la causa la <\/span><\/span>mioton\u00eda<\/span><\/span>, <\/span><\/span>que es<\/span><\/span> el<\/span><\/span> s\u00edntoma que define la enfermedad y <\/span><\/span>que hace que los pacientes <\/span><\/span>pued<\/span><\/span>a<\/span><\/span>n contraer el <\/span><\/span>m\u00fasculo,<\/span><\/span> pero<\/span><\/span> tengan mucha dificultad para <\/span><\/span>relajarlo.\u00a0<\/span><\/span><\/span><\/p>\n

\n
\n

Art\u00edculo de referencia: <\/strong>Xiomara Fern\u00e1ndez-Garibay, Mar\u00eda A. Ortega, Estefan\u00eda Cerro-Herreros, Jordi Comelles, Elena Mart\u00ednez, Rub\u00e9n Artero, Juan M. Fern\u00e1ndez-Costa and Javier Ramon. Bioengineered in vitro 3D model of myotonic dystrophy type 1 human skeletal muscle.<\/a><\/u> <\/span>Biofabrication (2021), 13 (3), 035035.<\/span><\/p>\n

\u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

Investigadores del IBEC liderados por Javier Ram\u00f3n y Juan M. Fern\u00e1ndez desarrollan el primer modelo tridimensional para la distrofia miot\u00f3nica, una enfermedad rara y sin cura. El modelo combina c\u00e9lulas de paciente y t\u00e9cnicas de bioingenier\u00eda y representa un gran avance con respecto a la utilizaci\u00f3n de animales y de cultivos celulares. Permitir\u00e1 dise\u00f1ar tratamientos personalizados y m\u00e1s efectivos, y testar futuros f\u00e1rmacos de una manera mucho m\u00e1s eficiente.<\/h3>\n","protected":false},"author":4,"featured_media":83864,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[97],"tags":[1486,1130,1488,1487],"post_formats":[],"class_list":["post-83878","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticias-de-investigacion","tag-distrofia-miotonica","tag-javier-ramon-es","tag-juan-m-fernandez-es","tag-xiomara-fernandez-es"],"yoast_head":"\nHacia un tratamiento para la distrofia miot\u00f3nica: primer modelo 3D con c\u00e9lulas de pacientes - Institute for Bioengineering of Catalonia<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ibecbarcelona.eu\/es\/hacia-un-tratamiento-para-la-distrofia-miotonica-primer-modelo-3d-con-celulas-de-pacientes\/\" \/>\n<meta property=\"og:locale\" content=\"es_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Hacia un tratamiento para la distrofia miot\u00f3nica: primer modelo 3D con c\u00e9lulas de pacientes - Institute for Bioengineering of Catalonia\" \/>\n<meta property=\"og:description\" content=\"Investigadores del IBEC liderados por Javier Ram\u00f3n y Juan M. 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