Descubren una molécula que abre un camino para combatir el Parkinson
Un grupo de investigadores del Conicet de Tucumán demostró en estudios in vitro que un derivado de un conocido antibiótico, la tetraciclina demeclociclina (DMC), tiene efectos protectores sobre las neuronas que se ven afectadas en la enfermedad de Parkinson (EP), lo que sienta las bases para avanzar a estudios preclínicos para comprobar si puede evitar la muerte de estas células y, de ese modo, detener la progresión de la patología que afecta al 1% de la población mayor a 65 años.
Se trata de una molécula desarrollada entre el Instituto de Investigación en Medicina Molecular y Celular Aplicada (IMMCA, Conicet-UNT-Siprosa), con base en Tucumán, y el Instituto del Cerebro de París (Francia), cuya investigación fue publicada recientemente en la prestigiosa revista Cells.
«De acuerdo a la literatura científica y a resultados de trabajos previos que realizamos con el grupo de investigación, sabíamos que hay algunas tetraciclinas (antibióticos que se usan para varias enfermedades) que tienen capacidades neuroprotectoras, lo que serviría para un uso potencial tanto para Parkinson como para Alzheimer que son las dos enfermedades que estamos investigando», explicó a Télam Rodrigo Tomas-Grau, coautor del estudio y becario posdoctoral del Conicet en IMMCA.
«Lo que nosotros hicimos junto al Instituto del Cerebro de París (Francia) fue sintetizar una nueva molécula a partir de la demeclociclina que no tiene capacidad antibiótica»Rodrigo Tomas-Grau, coautor del estudio y becario posdoctoral
«En ese contexto había un trabajo con demeclociclina que demostraba que esta molécula impedía que la proteína alfa-sinucleína (aS) -presente en unas células cerebrales llamadas dopaminérgicas- comience a agregarse de forma tóxica, que es lo que puede desencadenar el Parkinson, o sea que interfería en ese proceso».
Tomas-Grau explicó que «el problema es que las enfermedades como Parkinson y Alzheimer son enfermedades crónicas y progresivas, entonces no se puede medicar con antibióticos de por vida ya que conllevaría a otro problema que sería la resistencia a esos antibióticos».
«Lo que nosotros hicimos junto al Instituto del Cerebro de París (Francia) fue sintetizar una nueva molécula a partir de la demeclociclina que no tiene capacidad antibiótica, es decir que le modificamos un par de cosas de su estructura química para quitarle esa capacidad», describió.
Una vez que se obtuvo esa nueva molécula realizaron pruebas para ver si mantenía su capacidad neuroprotectora y descubrieron que no sólo continuaba esa propiedad, sino que era mejor aún que la demeclociclina original con capacidad antibiótica.
Además de interferir en la función tóxica de la proteína alfa-sinucleína (aS), las y los investigadores comprobaron en el instituto parisino que la molécula de demeclociclina que había creado tenía efectos antiinflamatorios sobre la neuronas que habían sido afectadas por la toxicidad de la proteína.
Florencia González Lizárraga, becaria posdoctoral del IMMCA y la otra coautora de este descubrimiento, señaló -por su parte- que el nuevo trabajo forma parte de un «ambicioso proyecto de investigación» financiado por la Agencia Nacional de Promoción Científica (ANPCyT), y que contó con un subsidio de la Asociación France Parkinson.
Los investigadores destacaron que los resultados sugieren que esta molécula puede ser una candidata prometedora como fármaco para el desarrollo de estudios preclínicos de la enfermedad de Parkinson en modelos animales.
Consultado sobre los siguientes pasos, Tomas-Grau señaló que «ésta es la primera fase, que es el desarrollo de la molécula y su prueba en tubos de ensayo y con células; con esta evidencia, el próximo paso sería comenzar a probar en modelos animales, esto es ratones transgénicos que poseen características de la enfermedad, lo que se llaman estudios pre-clínicos, para comprobar eficacia y seguridad».
Los resultados sugieren que esta molécula puede ser una candidata prometedora como fármaco para el desarrollo de estudios preclínicos de la enfermedad de Parkinson en modelos animales.
«Sólo después de haber sorteado exitosamente muchos de estos ensayos en organismos modelo de la enfermedad, podría ser candidata para ensayos en humanos. El camino es largo, pero dada la abundante evidencia del efecto neuroprotector de tetraciclinas, creemos que justifica seguir trabajando en esta dirección», indicó Tomas-Grau, quien también indicó que «más allá de este desarrollo seguimos en la búsqueda de nuevas moléculas; estamos haciendo el mismo camino con otras tres y estamos muy avanzados. Esta es una rueda de síntesis de nuevas moléculas que se van presentando al mundo para desarrollar estudios específicos y llegar a nuevos fármacos».
El estudio fue liderado por Rosana Chehín, doctora en Bioquímica e investigadora del Conicet en el IMMCA, y Bruno Figadère, de la Universidad de Paris-Sud Saclay, en Francia; también integran el grupo la doctora Raisman Vozari y Michael Patrick, quienes fueron clave en la articulación con Francia.
Qué es la Enfermedad de Parkinson
La Enfermedad de Parkinson fue descripta y caracterizada hace más de 200 años; sin embargo, al día de hoy no existe un fármaco capaz de detener o siquiera enlentecer el proceso de muerte neuronal, solamente están disponibles los de carácter paliativo que actúan aliviando los síntomas de la enfermedad.
Se trata de una afección degenerativa del cerebro asociada a síntomas motores (lentitud de movimientos, temblores, rigidez y desequilibrio) y a otras complicaciones como el deterioro cognitivo, los trastornos mentales, del sueño, el dolor y alteraciones sensoriales.
A nivel mundial, la discapacidad y las defunciones debidas a la enfermedad de Parkinson están aumentando más rápidamente que las de cualquier otro trastorno neurológico.
Según informó la Organización Mundial de la Salud, la prevalencia de la enfermedad de Parkinson se ha duplicado en los últimos 25 años y se estima que para 2030 podría volver a duplicarse.
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