CPEB alteration and aberrant transcriptome-polyadenylation lead to a treatable SLC19A3 deficiency in Huntington’s disease
Sara Picó, Alberto Parras, María Santos‐Galindo, Julia Pose‐Utrilla, Margarita Castro, Enrique Fraga, Ivó H. Hernández, Ainara Elorza, Héctor Anta, Nan Wang, Laura Martí‐Sánchez, Eulàlia Belloc, Paula Garcia‐Esparcia, Juan José Garrido, Isidró Ferrer, Daniel Macías‐García, Pablo Mir, Rafael Artuch, Belén Pérez, Félix Hernández, Pilar Navarro, José Luis López-Sendón, Teresa Iglesias, Xia Yang, Raúl Méndez, José J. Lucas
Abstract
cause biotin-thiamine–responsive basal ganglia disease (BTBGD), a striatal disorder that can be treated with a combination of biotin and thiamine. Similar to patients with BTBGD, patients with HD demonstrated decreased thiamine in the cerebrospinal fluid. Furthermore, patients and mice with HD showed decreased striatal concentrations of thiamine pyrophosphate (TPP), the metabolically active form of thiamine. High-dose biotin and thiamine treatment prevented TPP deficiency in HD mice and attenuated the radiological, neuropathological, and motor HD-like phenotypes, revealing an easily implementable therapy that might benefit patients with HD.