Oral trehalose shows promise as a treatment for mucopolysaccharidosis type II, reducing harmful accumulations and enhancing cognitive functions.
Researchers have found oral trehalose, a natural disaccharide, to significantly ameliorate symptoms associated with mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome. This lysosomal storage disorder results from the deficiency of the enzyme iduronate-2-sulfatase (Ids), leading to harmful accumulations of glycosaminoglycans (GAGs) within various organs, including the brain, and causing severe neurological and systemic symptoms.
Current therapeutic options for MPS II primarily involve enzyme replacement therapies (ERT), which, unfortunately, are unable to traverse the blood-brain barrier, severely limiting their effectiveness against neurological symptoms. Building on previous evidence demonstrating trehalose's neuroprotective abilities, researchers at Pusan National University Yangsan Hospital sought to explore its potential benefits when administered orally to Ids-deficient mice.
Over the course of 24 weeks, Ids knockout (KO) mice and wild-type controls were provided with drinking water containing 2% trehalose. The study aimed to assess trehalose’s impact on GAG accumulation, various histopathological changes, and behavior. Through histological evaluations, significant alterations were observed: Ids-KO mice treated with trehalose yielded reduced vacuolization and inflammation across several organs, including the brain, spleen, and liver.
"Oral administration of trehalose significantly suppressed GAG levels, vacuolization, inflammation and apoptosis," stated the authors of the article, underscoring its substantial effects on multiple tissues affected by GAG deposition.
Not only did trehalose treatment demonstrate reduced pathological changes at the cellular level, but it also correlated with improved cognitive functions, as evidenced by enhanced short-term spatial learning and working memory tested through the spontaneous alteration behavior Y-maze test. The treated Ids-KO mice displayed more exploratory behavior compared to those receiving only water, indicating notable improvements.
Despite these promising findings, no significant changes were reported concerning overall body weight or the relative weights of certain organs, such as the liver and spleen, throughout the treatment period. Researchers acknowledged the limitations, indicating the potential for long-term treatments to yield more noticeable physiological improvements.
These results align with previous studies demonstrating trehalose’s therapeutic effects against other lysosomal storage diseases, hence elevary its potential as part of multifaceted treatment strategies for MPS II, particularly for mitigating neurological deterioration.
Given the challenges associated with existing therapies targeting neurological symptoms—such as the need for regular infusions and the inability to effectively reach neural tissues—oral trehalose presents itself as an alternative approach worthy of consideration. “These results suggest oral trehalose can reduce GAG accumulation... and could be a promising treatment option for MPS II,” the authors concluded, expressing optimism for continued research.
Moving forward, the goal will be to conduct extensive studies to ascertain the full range of trehalose’s benefits, optimal dosing regimens, and effectiveness when combined with existing therapies, aiming to establish comprehensive treatment protocols for patients afflicted with MPS II.