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Consiguen por primera vez que la quimioterapia penetre en el cerebro para tratar tumores Hasta ahora era muy complicado tratar un tumor cerebral como el glioblastoma Getty Images
Ahora, científicos de Northwestern Medicine (Estados Unidos) han realizado el primer ensayo clínico en humanos que ha conseguido, a través de un dispositivo de ultrasonidos implantable en el cráneo, abrir la barrera hematoencefálica y penetrar en regiones críticas del cerebro para administrar quimioterapia .
La barrera hemotoencefálica se cierra al cabo de una hora El procedimiento para abrir la barrera hematoencefálica, que dura cuatro minutos , se realiza con el paciente despierto , que se va a casa al cabo de unas horas. Según sus resultados, publicados en la revista científica 'The Lancet Oncology', muestran que la apertura de la barrera hematoencefálica multiplica por cuatro o por seis las concentraciones del fármaco en el cerebro humano. El tratamiento es seguro y bien tolerado , y algunos pacientes reciben hasta seis ciclos de tratamiento.
Los científicos observaron este aumento con dos potentes fármacos quimioterapéuticos diferentes, el paclitaxel y el carboplatino . Estos fármacos no se utilizan en la actualidad para tratar a estos pacientes porque no atraviesan la barrera hematoencefálica en circunstancias normales. La temozolomida, la quimioterapia utilizada actualmente para el glioblastoma, atraviesa la barrera hematoencefálica, pero es un fármaco débil.
Además, este es el primer estudio que describe lo rápido que se cierra la barrera hematoencefálica tras la sonicación (aplicación de ultrasonidos).
Los científicos descubrieron que la mayor parte del restablecimiento de la barrera hematoencefálica se produce en los primeros 30 a 60 minutos tras la sonicación . Según los autores, los resultados permitirán optimizar la secuencia de administración del fármaco y la activación de los ultrasonidos para maximizar la penetración del fármaco en el cerebro humano.
"Se trata de un avance potencialmente enorme para los pacientes con glioblastoma", ha asegurado el líder del estudio, Adam Sonabend, profesor asociado de Cirugía Neurológica de la Facultad de Medicina Feinberg de la Universidad Northwestern y neurocirujano del mismo centro.
La barrera hematoencefálica es una estructura microscópica que protege al cerebro de la inmensa mayoría de los fármacos circulantes. En consecuencia, el repertorio de fármacos que pueden utilizarse para tratar enfermedades cerebrales es muy limitado.
Los pacientes con cáncer cerebral no pueden ser tratados con la mayoría de los fármacos que son eficaces contra el cáncer en otras partes del cuerpo, ya que no atraviesan la barrera hematoencefálica . La reutilización eficaz de fármacos para tratar patologías cerebrales y cáncer requiere su administración en el cerebro.
En el pasado, los estudios que inyectaron paclitaxel directamente en el cerebro de pacientes con estos tumores observaron signos prometedores de eficacia, pero la inyección directa se asoció a toxicidad como irritación cerebral y meningitis .
Los científicos descubrieron que la apertura de la barrera hematoencefálica mediante ultrasonidos y microburbujas es transitoria, y que la mayor parte de la integridad de la barrera hematoencefálica se restablece una hora después de este procedimiento en humanos.
"Hay una ventana temporal crítica tras la sonificación en la que el cerebro es permeable a los fármacos que circulan por el torrente sanguíneo", ha afirmado Sonabend.
Estudios anteriores en humanos demostraron que la barrera hematoencefálica se restablece por completo 24 horas después de la sonicación cerebral y, basándose en algunos estudios en animales, se suponía que la barrera hematoencefálica está abierta durante las primeras seis horas aproximadamente. Este nuevo estudio demuestra que este plazo podría ser más corto.
Otra primicia del estudio es que el uso de una novedosa rejilla implantable en el cráneo con nueve emisores de ultrasonidos diseñada por la empresa francesa de biotecnología Carthera abre la barrera hematoencefálica en un volumen de cerebro nueve veces mayor que el dispositivo inicial (un pequeño implante de un solo emisor de ultrasonidos).
Esto es importante porque, para ser eficaz, este enfoque requiere la cobertura de una amplia región del cerebro adyacente a la cavidad que queda en el cerebro tras la extirpación de los tumores de glioblastoma.
Hay un nuevo estudio en marcha combinando fármacos para luchar contra el glioblastoma Los resultados del estudio constituyen la base de un ensayo clínico de fase 2 que los científicos están llevando a cabo en pacientes con glioblastoma recurrente.
El objetivo del ensayo, en el que los participantes reciben una combinación de paclitaxel y carboplatino administrada en el cerebro con la técnica de ultrasonidos, es investigar si este tratamiento prolonga la supervivencia de estos pacientes. La combinación de estos dos fármacos se utiliza en otros tipos de cáncer, lo que constituye la base para combinarlos en el ensayo de fase 2.
En el ensayo clínico de fase 1, los pacientes se sometieron a cirugía para la resección de sus tumores y la implantación del dispositivo de ultrasonidos. Comenzaron el tratamiento pocas semanas después de la implantación.
Los científicos aumentaron la dosis de paclitaxel administrada cada tres semanas con la consiguiente apertura de la barrera hematoencefálica mediante ultrasonidos. En subconjuntos de pacientes, se realizaron estudios durante la cirugía para investigar el efecto de este dispositivo de ultrasonidos en las concentraciones del fármaco. La barrera hematoencefálica se visualizó y cartografió en el quirófano mediante un dado fluorescente llamado fluoresceína y por resonancia magnética obtenida tras el tratamiento con ultrasonidos.
"Aunque nos hemos centrado en el cáncer, esto abre la puerta a investigar tratamientos novedosos basados en fármacos para millones de pacientes que padecen diversas enfermedades cerebrales", ha remachado Sonabend.
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