Oral trehalose improves histological and behavior symptoms of mucopolysaccharidosis type II in iduronate 2-sulfatase deficient mice

Mucopolysaccharidosis type II (MPS II) is caused by a deficiency in iduronate-2-sulfatase (Ids), an enzyme that catabolizes glycosaminoglycan (GAG). Ids insufficiency results in the accumulation of GAG in various organs, ultimately resulting in multisystemic disease. Trehalose, a non-reducing disaccharide, has shown protective effects against various diseases. However, its potential utility through oral administration in MPS II has not yet been explored. In the present study, to investigate the efficacy of oral trehalose in Ids-knock-out (KO) mice, Ids-KO and wild type (WT) mice were treated with 2% trehalose dissolved in distilled water ad libitum for 24 weeks. Histological analysis revealed that almost all tissues from Ids-KO mice exhibited abnormal changes, including large vacuolization, inflammatory cell infiltration, and GAG deposition. However, oral administration of trehalose significantly suppressed GAG levels, vacuolization, inflammation and apoptosis in the spleen and brain. Additionally, oral trehalose considerably improved cognitive functions, such as short-term spatial learning and working memory, alongside limited improvements in walking capacity in Ids-KO mice. These results suggest that oral trehalose can reduce GAG accumulation, vacuolization and the number of apoptotic and inflammatory cells in pathological tissues including the brain, ultimately considerably improving spontaneous alteration behavior and could be a promising treatment option for MPS II.