Terapia génica como potencial tratamiento para la osteopetrosis maligna

Autores

Resumen

La osteopetrosis maligna es una enfermedad rara, y Costa Rica se sitúa con la incidencia más alta del mundo con 3,4 casos por cada 100 000 nacimientos comparada con 1 caso por cada 250 000 nacimientos a nivel mundial. Por lo tanto, es de vital importancia conocer los avances en el diagnóstico y nuevas terapias que puedan surgir.

Al tratarse de una enfermedad rara, los avances han sido escasos en los últimos años, y el tratamiento se limita actualmente al trasplante de células madre hematopoyéticas. Sin embargo, en algunos casos esta terapia no se puede aplicar por falta de donantes HLA idénticos, y presenta complicaciones asociadas como la enfermedad de injerto versus hospedero y el rechazo agudo. Recientemente, se han presentado nuevas aplicaciones de la terapia génica como una potencial herramienta curativa para estos pacientes. Con el uso de vectores lentivirales y mediante métodos ex vivo, se desarrolla un ensayo clínico en fase I; de esta manera se está a la expectativa de posibles resultados favorables para su aplicación futura en fases clínicas avanzadas.

En esta revisión, se abordan aspectos generales de esta patología, así como las estrategias terapéuticas convencionales, culminando con el diseño de modelos animales y experimentales en fase clínica de prueba para vectores virales que acarrean los genes que corrigen los defectos genéticos implicados.

Palabras clave

Abstract

Malignant osteopetrosis is a rare disease, and Costa Rica has the highest incidence with a rate of approximately 3.4 out of every 100,000 births compared with 1 out of every 250,000 births around the world. Updates and advances in diagnosis and new therapies in the future is crucial. Since it has been classified as a rare disease, in recent years progress has been limited.  Hematopoietic Stem Cell Transplantation is the first line treatment.

However, in some cases this therapy cannot be useful due to the lack of HLA-identical donors and associated complications such as graft versus host disease and acute rejection. New applications of gene therapy have recently been arising as a potential curative treatment for these patients. With lentiviral vectors and ex vivo methods, with a phase I clinical trial in progress, favorable results are expected for its future application in advanced clinical phases. In this review, we describe general aspects of this disease, and the conventional therapeutic strategies. We will analyze the design of animal and experimental models in the clinical trial phase I for viral vectors that carry the genes that correct the genetic defects involved.

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Referencias

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