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Investigadores desarrollan un parche genético para prevenir la sordera hereditaria

La sordera hereditaria puede manifestarse de diferentes formas. A menudo, el defecto hereditario (mutación) provoca inmediatamente sordera desde el nacimiento. A veces, como con DFNA9, experimenta los problemas iniciales de audición después de cuarenta, cincuenta, sesenta años. Esto tiene mucho que ver con la forma en que DFNA9 funciona mecánicamente. Cada persona obtiene la mitad de sus genes de su padre y la otra mitad de su madre. Si tiene dos copias sanas del gen DFNA9, su oído interno funciona normalmente. Si recibe una copia mutada del gen de su padre o de su madre, la sordera se desarrollará más adelante en la vida.

Espaguetis proteicos

Erik de Vrieze y Erwin van Wijk, ambos investigadores de Hearing & Genes del departamento de oído, nariz y garganta, han realizado una extensa investigación sobre la afección. De Vrieze: “Ahora sabemos que en realidad se produce suficiente proteína DFNA9 asociada con una sola copia genética sana para poder oír bien de por vida. Pero hay un problema con esta afección. La proteína mutada es, en cierto modo, perturbando la función de la proteína saludable, que se adhiere a ella, de modo que la proteína saludable tampoco puede hacer más su trabajo.

Las células del oído interno eliminan constantemente este espagueti de proteínas agrupadas, pero después de décadas, el servicio de limpieza de estas células está llegando a su límite y ya no puede hacer frente a estas acumulaciones de proteínas. Se supera un valor umbral. Como resultado, los desechos se acumulan, las células auditivas comienzan a funcionar mal e incluso mueren con el tiempo. Después de años de audición normal, los pacientes con DFNA9 notan repentinamente que su audición se está deteriorando y, a veces, se deteriora muy rápidamente. Hasta que en algún momento se volverán sordos. “

Tiempo suficiente para el tratamiento

La mutación específica de DFNA9parece tener su origen en un ancestro común en el sur de los Países Bajos, en algún lugar al final de la Edad Media. Esto se puede deducir más o menos de la propagación de la manifestación clínica bastante única, que ahora se estima que ocurre en aproximadamente 1500 personas en los Países Bajos (sur) y Bélgica. Quizás incluso más importante que el origen de la enfermedad es si se puede hacer algo al respecto.

“Esta condición tiene dos características favorables para el desarrollo de la terapia. En primer lugar, es una afección hereditaria que solo se manifiesta después de algunas décadas de vida. En caso de que se disponga de un tratamiento eficaz para esta enfermedad, se dispone de un período de tiempo suficientemente amplio para aplicarlo antes de que la pérdida auditiva realmente se produzca.” – Erwin van Wijk, investigador –

Desactivar el gen mutante

El otro punto, desarrollar una terapia eficaz, es un poco más complicado, pero ofrece buenos puntos de partida. Van Wijk: “La idea es que al desactivar específicamente la copia del gen mutado se puede prevenir la sordera. Sin esta copia del gen mutado, no se producirá ninguna proteína mutante y ya no se producirá el agrupamiento de proteínas. Además, una sola copia de un gen sano produce suficiente proteína para mantener una buena audición “.

Parche genético

De Vrieze y Van Wijk desarrollaron aún más esta idea. Junto con sus colegas, ahora han publicado los resultados de la investigación en la revista científica Molecular Therapy – Nucleic Acids. “Los genes, que residen en nuestro ADN, proporcionan el código genético para el proceso de traducción en proteínas“, dice De Vrieze. “Para pasar de un gen a una proteína, siempre se necesita un proceso de traducción a través del llamado ARN mensajero. Y ese es exactamente el proceso en el que nos enfocamos. El error de ADN único en el gen DFNA9 también se refleja en el ARN. Desarrollamos una pequeña porción de ARN que se une específicamente al ARN mensajero derivado del gen DFNA9 mutado. Como resultado, todo el ARN mensajero mutado se dirige a la degradación. De esta manera, se pierde un enlace esencial y la proteína DFNA9 mutante ya no es o apenas producido.


En los últimos años, De Vrieze y Van Wijk no solo han desarrollado este parche genético, sino que también han investigado su efecto en células cultivadas. Su artículo actual describe principalmente estos resultados, ya que el enfoque funciona en células cultivadas. Entonces hay una “prueba de concepto”, como se le llama en ciencia. En resumen, la investigación muestra que el enfoque funciona a nivel celular.

Arthur Robbesom de la Fundación “El Noveno de …” DFNA9 está encantado con el estudio. “Esto ofrece una perspectiva real para unas 1.500 personas en los Países Bajos y Bélgica que padecen esta afección”. La fundación también participa de cerca en esta investigación. Robbesom: “Ahora es importante dar los siguientes pasos necesarios en la investigación lo antes posible. Le apoyaremos de todo corazón”.

Fuente: Infoacufenos.com


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