Abstract: Ataxia-telangiectasia is a rare neurodegenerative disease with a complex phenotype, which has recently been associated with alterations in metabolism, inadequate responses to oxidative stress and inflammation, as well as increased cardiovascular and tumor risk. All of these appear to be attributable to genetic mutations/variants in the ataxia-telangiectasia mutated gene, which encodes the ataxia-telangiectasia mutated protein. The possibility of a better phenotypic definition provides a basis for timely, personalized therapeutic intervention to reduce or prevent worsening of clinical symptoms. Several ataxia-telangiectasia mutated knock-out murine models were created, but none efficiently developed progressive ataxia, failing to recapitulate human neurodegeneration following ataxia-telangiectasia mutated deficiency. Furthermore, considering the strong awareness of the ban on the use of animals in scientific research, a great effort has been made and is still ongoing to create human cellular models of ataxia-telangiectasia with the aim of understanding in detail the molecular mechanisms of neurodegeneration and skeletal muscle defect, of being able to identify specific therapies. This review highlights human stem cell approaches as in vitro models that have been established as attempts to study the outcomes of ataxia-telangiectasia mutated inactivation regarding neurogenic and myogenic differentiation. The first attempts at differentiation from fetal tissues, through the induced pluripotent stem cell revolution and the latest urine-derived stem cells will be reviewed.

Key words: ataxia-telangiectasia, ataxia-telangiectasia mutated, genetic disease, in vitro cell modeling, neurodegenerative disorders, neurons, rare disease, skeletal muscle cell, stem cells, urine-derived stem cell