Enfermedad de Huntington y panorama actual de las estrategias terapéuticas.
Palabras clave:
Enfermedad de Huntington, huntingtina, terapia molecular dirigida, enfermedad neurodegenerativa, HTT, exón.Resumen
La enfermedad de Huntington (EH) es un trastorno neurodegenerativo con patrón de herencia autosómico dominante y una prevalencia mundial de 4,88 por cada 100.000 personas. El gen asociado es HTT, que codifica la proteína huntingtina. La mutación consiste en una expansión de trinucleótidos en HTT, que produce la huntingtina mutada (mHtt), la cual, mediante diferentes mecanismos moleculares, induce la muerte neuronal y la neurodegeneración. Por ello, la mHtt se ha convertido en un blanco de la terapéutica actual para la EH. Entre las principales estrategias se encuentran los moduladores del splicing, el ARN de interferencia y los oligonucleótidos antisentido. Otras terapias buscan modificar el ambiente intra y extracelular, el ADN y el reemplazo celular; entre estas se incluyen la terapia redox, la terapia dirigida por anticuerpos neutralizantes, los dedos de zinc, CRISPR, la reparación del ADN y la inducción de células pluripotenciales. El objetivo de esta revisión es abordar las terapias emergentes para el tratamiento de la EH, según su mecanismo fisiopatológico. Actualmente existe un panorama adecuado sobre las terapias modificadoras de la EH; sin embargo, es necesario avanzar en sus estudios para llevarlas a un contexto clínico seguro y confiable, de modo que los pacientes puedan beneficiarse.
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Derechos de autor 2026 Jaime Alberto Herrera, Nicolas Laverde-Sudupe, Sofía Gómez-González, Sara Castro-Sandino, Angela Lizeth Giraldo-Serna, Elizabeth Londoño-Velasco
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