Short Review: Investigating ARSACS: models for understanding cerebellar degeneration

Autores de CIPF

• Ana Artero Castro

  Autor

• Candela Machuca Arellano

  Autor

• 

  Francisco Rodríguez Jiménez

  Autor

• 

  Slaven Erceg Vukicevic

  Autor

Participantes ajenos a CIPF

• Jendelova P

Grupos de Investigación

• Laboratorio de Enfermedades Raras Neurodegenerativas

• Laboratorio Terapias con Células Madre en Enfermedades Neurodegenerativas

  

  Jefe/a de Grupo

  Slaven Erceg Vukicevic

Abstract

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease that includes progressive cerebellar dysfunction. ARSACS is caused by an autosomal recessive loss-of-function mutation in the SACS gene, which encodes for SACSIN. Although animal models are still necessary to investigate the role of SACSIN in the pathology of this disease, more reliable human cellular models need to be generated to better understand the cerebellar pathophysiology of ARSACS. The discovery of human induced pluripotent stem cells (hiPSC) has permitted the derivation of patient-specific cells. These cells have an unlimited self-renewing capacity and the ability to differentiate into different neural cell types, allowing studies of disease mechanism, drug discovery and cell replacement therapies. In this study, we discuss how the hiPSC-derived cerebellar organoid culture offers novel strategies for targeting the pathogenic mutations related to ARSACS. We also highlight the advantages and challenges of this 3D cellular model, as well as the questions that still remain unanswered.

Keywords

• 3D organoids; ARSACS; ataxia; cerebellum; disease modelling; induced pluripotent stem cells