SHANK3-Primary-antibodies-ab136429-6

Una cura para las enfermedades raras

Cuando se habla de las enfermedades raras suele darse con frecuencia lo siguiente: por un lado alguien argumenta que por muy triste que sea la situación de los pacientes que las sufren, no hay recursos suficientes como para que una sociedad se permita gastar dinero y esfuerzo en estudiarlas todas. Por otro lado, alguien que conoce el mundo de la investigación insiste en que todas las enfermedades, sea cual sea la frecuencia con que se presenten en la sociedad, tienen una misma base biológica y por tanto el estudio de cualquiera de ellas beneficia al progreso en la lucha contra cualquier patología.

Al final estas afirmaciones se repiten tanto que acaban convirtiéndose en mantras un poco huecos, así que lo mejor será poner un ejemplo concreto y representativo, y que el lector pueda decidir si hay más beneficios que perjuicios en el estudio y la investigación de las enfermedades raras, por muy complicado que sea (y ciertamente lo es) gestionar los ya de por sí escasos recursos de los que la investigación biomédica moderna puede disponer.

La recién creada asociación de afectados por el síndrome de Phelan-McDermid pretende mejorar la vida de los pacientes poniendo en contacto a las familias de los afectados y facilitando así el seguimiento de la enfermedad por parte de clínicos e investigadores (fuente:http://www.22q13.org.es)

 El ejemplo en cuestión es el síndrome de Phelan-McDermind. Un síndrome que personalmente, y pese a haber pasado cinco años trabajando en el campo de la investigación en enfermedades raras, desconocía. Este es uno de los problemas a los que se enfrentan los pacientes: no el que yo desconozca cosas (ese es problema mío y sigo trabajando en ponerle solución), sino que hay tantas enfermedades catalogadas como raras y se conoce tan poco de algunas de ellas, que incluso entre profesionales de la medicina o la investigación biomédica es imposible conocer ni una fracción significativa de todas ellas. Esto da pie a dificultades en el diagnóstico que obviamente perjudican al paciente, pero además hacen muy difícil el seguimiento del número real de afectados.  Y esto afecta también al conocimiento de la enfermedad: en investigación científica no se puede sacar ninguna conclusión si no se dispone de datos que analizar. Cuantos más pacientes se diagnostiquen y mejor se conozca qué síntomas son comunes o diferenciadores, más sencillo es establecer unos criterios más adecuados para diagnóstico y tratamiento.

cromosoma

En este esquema se puede observar cómo el típico cromosoma que parece un señor patilargo levantando los brazos (el nombre técnico para los brazos es “cromátidas”), está formado por un ovillo de ADN, la famosa doble hélice que se ve detallada a la derecha (fuente: http://recursostic.educacion.es/ciencias/biosfera/web/alumno/4ESO/genetica1/contenidos4.htm)

Esto último es muy relevante en el caso concreto de la enfermedad que estamos usando como ejemplo. Bajo la denominación de “síndrome de Phelan-McDermid”se aglutina un conjunto de síntomas neurológicos, relacionados en algunos casos con patologías del tipo del autismo. Estos síntomas correlacionan con defectos en la información genética contenida en un lugar muy concreto del genoma. Recordemos que en nuestra especie, el genoma (es decir, el conjunto de todos los genes que sirven como instrucciones para controlar nuestro organismo) se compone de 23 pares de cromosomas. Un cromosoma, simplificando bastante, podría definirse como una especie de varilla alargada formada por una única (pero muy larga) molécula de ADN enrollada sobre sí misma. El extremo de esta varilla se puede romper, y los genes que contenga se perderán para siempre. Esta rotura se produce de manera que el cromosoma sigue siendo funcional en su mayor parte, todavía capaz de replicarse y transmitirse, perpetuándose en la descendencia del individuo portador. Todos los afectados de este síndrome presentan una pérdida de material genético en una misma zona concreta: el brazo largo del cromosoma 22. Como además es una zona amplia, hay gran heterogeneidad de síntomas que se corresponden con  pérdidas mayores o menores de material genético. La pregunta obvia sería: ¿qué hay en ese extremo del cromosoma 22?

PhelanMcDermid_cariotipo

En una muestra de cromosomas provenientes de un afectado por el síndrome de Phelan-McDermid se observa un defecto en el cromosoma 22, señalado por la flecha (fuente: https://sfari.org/news-and-opinion/conference-news/2011/phelan-mcdermid-syndrome-foundation-2011/first-ever-phelan-mcdermid-meeting-has-its-eureka-moments)

Lo único que se sabe hasta el momento, es que en dicha región se localiza la información para construir una proteína llamada SHANK3. Dicha proteína, de algún modo todavía desconocido, es de capital importancia para que se formen las conexiones neuronales necesarias para el correcto desarrollo de muchas funciones cognitivas implicadas en procesos de aprendizaje. Un sistema nervioso formado por células donde las instrucciones necesarias para construir SHANK3 se han perdido, no está completo del todo y los niños que nacen con esta deficiencia muestran un retraso en procesos de aprendizaje tan importantes como el habla o la psicomotricidad más básica.Esta es la base molecular de la enfermedad: entendiéndola, es fácil comprender la heterogeneidad de síntomas que mencionábamos al principio. No es lo mismo que falte un trocito pequeño del cromosoma, que uno grande, del mismo modo que no es lo mismo que falte una página del libro de instrucciones, que un capítulo entero. Adyacentes al gen que da lugar a SHANK3 habrá regiones posiblemente implicadas en su propia regulación génica. Tal vez en los casos más graves, donde el retraso neurológico es más severo, falten más proteínas además de SHANK3. Gracias a que hoy día disponemos de mucha información en cuanto a qué tipo de instrucciones hay en cada región del genoma (aunque nos falta mucho por refinar),  podemos ir deduciendo qué páginas faltan y observar su correspondencia con los efectos a nivel molecular y celular: pero necesitamos muestras y resultados reproducibles. De nuevo, sin muchos casos en los que fijarnos, no podemos extraer conclusiones.

SHANK3-Primary-antibodies-ab136429-6

En esta neurona se ha teñido de color verde la proteína SHANK3, con lo que se puede apreciar lo omnipresente que se halla en todos los puntos de conexión (sinapsis) entre dicha neurona y otras vecinas (fuente:http://www.abcam.com/shank3-antibody-ab136429.html)

 Volvamos ahora a la faceta más social del problema: imaginemos la cantidad de niños con un retraso cognitivo no demasiado drástico, que tal vez nunca lleguen a saber que su problema es en realidad una pequeña ausencia de material genético en su cromosoma 22. ¿Deberíamos encogernos de hombros y lamentar que la genética humana sea tan amplia e inabarcable? ¿Suspirar pensando que nuestros sistemas sanitarios jamás podrán cubrir todas las necesidades de diagnóstico para tantos y tan diversos trastornos genéticos? Más bien al contrario. Las asociaciones de pacientes y su colaboración estrecha con organismos investigadores, proporcionando los unos una provisión valiosísima de datos para analizar y los otros un atisbo de esperanza en cuanto a acelerar el conocimiento de porqué sufren sus síntomas y adelantar una posible mejora, son un precioso ejemplo de esfuerzo colaborativo. Además de simbolizar de manera rotunda el auténtico poder de la ciencia como instrumento para mejorar nuestra vida en sociedad, con un diálogo continuo, cercano y de doble sentido que facilita el rápido avance de la investigación y el inmediato retorno del beneficio para los afectados más directos.

Y para terminar, usemos un poco la imaginación, porque sin ella jamás podremos explotar del todo el poder de la ciencia como herramienta. Imaginemos que tras años y años de estudio y conocimiento hemos averiguado todos y cada uno de los detalles genéticos escondidos en los 23 pares de cromosomas humanos. Que sabemos comprender los complejos mapas sinápticos que utilizan nuestras células cerebrales para componer nuestro sistema nervioso y nuestra compleja mente. Que controlamos los genes que tornan las células maleables, permitiéndonos manipularlas para evitar que se produzcan tumores, o incluso convertirlas en células distintas para recomponer tejidos dañados. Con este tipo de logros y otros que aún no podemos ni siquiera imaginar, no habría enfermedad que pudiese arrebatarnos nuestros recuerdos, nuestra mente, nuestra capacidad para relacionarnos con los demás. En ese hipotético caso, no importaría en absoluto detectar en nuestros hijos cualquier fallo en sus genes, pues tendríamos las herramientas suficientes como para entender el problema al que nos enfrentamos, y solucionarlo.

La buena noticia: muchas de estas herramientas ya están a nuestro alcance. La mala: que todavía queda mucho tiempo para llegar a esta situación aparentemente utópica. Pero debería reconfortarnos el hecho de que todas estas herramientas y estrategias en realidad se funden en una sola: el conocimiento. Tal vez podamos algún día decir que fue el conocimiento lo que supuso una cura para todas las enfermedades, raras o no. Así que, tal vez, menospreciarcualquier estrategia encaminada a conocer mejor un problema, por raro, minoritario o poco frecuente que sea… suponga retrasar un poquito más la llegada de un futuro mejor para todos. Porque todos tenemos un cromosoma 22, así como otros tantos cromosomas llenos de información. A todos nos conviene conocer lo mejor posible qué secretos esconden todavía.

Este artículo ha sido escrito por Carlos Romá Mateo como colaboración con Raras pero no invisibles. Podéis seguirlo en @DrLitos o http://jindetres.blogspot.com.es/

 

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