Ahora es el turno de las proteínas

En principio la investigación necesita más cabezas que medios

Severo Ochoa

La idea de catalogar todas las proteínas humanas era la continuación natural a la caracterización de los genes acometida con el Proyecto Genoma Humano, y así se planteó a mediados de la década de 1990, en pleno trabajo de secuenciación. Las implicaciones biomédicas que pueden derivarse de la lectura de las proteínas, las moléculas que, junto con los metabolitos, definen la acción celular, son extensas.

¿Por qué ha tardado tanto en arrancar el Proyecto Proteoma Humano (HPP)? Además de la necesaria maduración tecnológica, una de las causas de que se haya dilatado tanto en el tiempo es la complejidad de la tarea, que pretende identificar las proteínas codificadas por los 20.300 genes humanos, cuantificarlas en las 230 estirpes celulares que integran nuestro organismo y definir sus modificaciones en las enfermedades más prevalentes (cáncer, cardiovasculares, neurodegenerativas).

Desde que surgió la idea, la HUPO tenía claro que una empresa así debía repartirse en laboratorios de todo el mundo. Algunos de ellos estarán en España. La estrategia adoptada es una aproximación cromosómica: los consorcios formados trabajarán en las proteínas codificadas por todos los genes agrupados en los diferentes cromosomas, y España junto con Suecia integra el grupo que se centrará en el cromosoma 19.

La enfermedad de Alzheimer y ciertos tipos de cáncer (ovario, páncreas y mama, entre otros) son algunas patologías que se han asociado a este cromosoma. La condición para incorporarse al consorcio es el manejo de una tecnología proteómica específica, la espectrometría de masas MRM (monitorización selectiva de iones), que deberá implantarse entre los grupos españoles, donde aún es minoritaria.

La presentación de la iniciativa de la HUPO ha sido uno de los platos fuertes del congreso de la Sociedad Española de Proteómica, coordinado por Concha Gil, catedrática de Microbiología de la Universidad Complutense, y Juan Pablo Albar, responsable de ProteoRed-ISCIII, del Centro Nacional de Biotecnología (CSIC). El congreso ha reunido en Segovia, con el décimo aniversario de la publicación del genoma coleando, a una importante representación de los grupos europeos y norteamericanos que trabajan en proteómica, y eso incluye también a los clínicos.

El mapeo y caracterización de proteínas sólo tienen sentido si repercute en la salud humana y para ello es preciso que se aporte un contexto fisiopatológico. Así, lo subraya Connie Jiménez, del Laboratorio de Onco-Proteómica en el Centro Médico Universitario de Ámsterdam. Ella investiga en biomarcadores proteicos en cáncer.

El papel de los biobancos
Donde más resultados está obteniendo es en el de colon, precisamente gracias a que el biobanco de ese tumor es de los más desarrollados en su hospital. Con ayuda de la espectrometría de masas ha revelado unos marcadores asociados a enfermedad inflamatoria intestinal y a cáncer colorrectal. Aunque están pendientes de publicación y no puede dar nombres, esos biomarcadores podrían ser útiles para discriminar el adenoma del carcinoma de colon. De esta forma contribuirían a la detección de las lesiones premalignas. “Nuestro objetivo es no sólo diagnosticar precozmente el cáncer, sino también ayudar en los cribados de las personas con alto riesgo, para reducir los falsos positivos de las colonoscopias”.

Más concreto se muestra Francisco Blanco, responsable de investigación del Instituto de Investigación Biomédica/Chuac. Este reumatólogo lleva trabajando casi dos décadas en la artrosis. Aunque se considera un “recién llegado” a la proteómica, dirige una iniciativa pionera que va a culminar con el desarrollo de un array de proteínas para el diagnóstico de la artrosis.

Su trabajo es un buen ejemplo de la traslación de hallazgos proteómicos. “Este año validaremos el array para la detección de la artrosis de rodilla en la fase asintomática y prerradiográfica”, explica. Los biomarcadores, unas cien proteínas que miden la destrucción del cartílago articular, o bien proceden de la membrana sinovial y del hueso subcondral, se validan primero en pacientes con el diagnóstico de gonartrosis. “El siguiente paso es emplearlos en población joven que ha recibido un reemplazo de menisco y por ello, está en riesgo de sufrir artrosis en unos años”.

La utilidad de los marcadores proteómicos en la clínica dependerá de que se hagan buenas clasificaciones de los pacientes; aquí el trabajo de los médicos y la suma de un amplio número de muestras es esencial. “Lo que antes era una enfermedad sola se está descomponiendo en diferentes fenotipos. El concepto no es un biomarcador para una enfermedad, sino para grupos de enfermos. Y ése es el reto”.

Fuente:www.diariomedico.com

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