Direct reprogramming of somatic skin cells from a patient with Huntington's disease into striatal neurons to create models of pathology

Abstract

A new in vitro model of Huntington's disease (HD) has been developed, based on the direct reprogramming of dermal fibroblasts from patients with the disease into striatal neurons. Direct reprogramming makes it possible to obtain neurons, preserving the epigenetic information inherent in the cells of a specific donor, and, consequently, the age-associated phenotype of the disease. The new model resembles the main histopathological feature of Huntington's disease – the accumulation of aggregates of the mutant huntingtin protein in striatal neurons obtained from the patient's fibroblasts. Conducting experiments on induced neurons from patients in culture, obtained using direct reprogramming, allows us to individually assess the degree of progression of neuropathology and implement a personalized approach in choosing a treatment strategy and selecting drugs for therapy. The in vitro model of Huntington's disease can be used for preclinical drug studies, for the treatment of neurodegenerative diseases and for assessing their effectiveness on neurons of specific patients.