Inhibidores de la monoamina oxidasa, posibilidad en el abordaje de demencias

Vivimos en una sociedad profundamente dependiente de la ciencia y la tecnología, y en la que nadie sabe nada de estos temas.

Carl Sagan

BIOSPAIN 2010

(VII)

En una mesa redonda sobre nuevos desarrollos clínicos en Alzheimer, varias compañías biotecnológicas españolas han expuesto resultados de los ensayos que tienen en desarrollo. Tamara Maes, directora científica de Orizon Genomics, ha explicado su programa de desarrollo de biomarcadores tempranos en demencias.

La especialista ha señalado hacia la carboxi-terminal ubiquitin-esterasa L1 (UCHL-1) en relación al desarrollo de demencia con cuerpos de Lewy, Alzheimer y Parkinson, y ha destacado la importancia del alelo 193M en la detección precoz.

Además, ha añadido un vínculo con NRSF/REST (factor silenciador restrictivo de neuronas), y ha concretado que sus niveles están inversamente relacionados con UCHL-1, según se ha comprobado en estudios sobre el cortex prefrontal. También cree que REST está ligado a la enfermedad de Huntington, ya que causa un descenso en la transcripción de genes neuronales, entre los que se incluyen BDNF.
LSD1, MAO-B, GSK-3…

Orizon Genomics trabaja con el modelo de C. elegans, lo que le ha permitido hallar genes patológicos que se correlacionan con homólogos en humanos. LSD1 modifica la metilación de lisina e inactiva p53, impidiendo la interacción de éste con otras proteínas. Las posibilidades de la inhibición farmacológica de LSD1 con bloqueadores de las monoaminas oxidasas (MAO-B), como Parnate, pueden ser diversas, gracias a que afecta a más genes como el citado UCHL-1, GDF15 y Notch. Estos inhibidores presentan buenos datos al atravesar la barrera hematoencefálica. Maes cree que pueden ser útiles en Parkinson usados en combinación con otros inhibidores de MAO-B.

Por su parte, Teodoro del Ser, director de Desarrollo Preclínico de Noscira, ha explicado los ensayos con tideglunib, inhibidor de GSK-3. En Alzheimer ya ha acabado un estudio en fase IIa en concomitancia con inhibidores de AChE, que permite claras mejoras frente a placebo (en 38 pacientes frente a sólo 12 con placebo).

Fuente: www.diariomedico.com

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