Trehalose

Trehalose is a natural disaccharide sugar, commonly used in the food industry for its ability to preserve the freshness and texture of food products. Known for its safety, trehalose has been widely consumed for many years without significant adverse effects (link). In recent years, there has been growing interest in trehalose as a therapeutic agent, particularly in the context of neurodegenerative and neuromuscular disorders (summarized here). Since 2004, studies have explored its potential benefits in various diseases and models, including Alzheimer's, Parkinson's, and Huntington's diseases, where it has shown promise in alleviating symptoms and slowing progression.  

HSPB8 myopathy is characterized by a gain of function mutation in one of the two copies of the HSPB8 gene (first described here). The wild type HSPB8 protein is protein is an important player in cellular autophagy machinery – a part the CASA complex. The mutation results in one healthy and one dysfunctional copy of the HSPB8 protein. The healthy copy exerts its physiological role in autophagy regulation, but at reduced capacity, leading to impaired autophagy. The dysfunctional HSPB8 protein forms insoluble aggregates, which accumulate in the cell, are harmful, and lead to cell death.  

Key Facts about Trehalose

Key Publications

Yap et al, 2023

This systemic review summarizes the animal studies of trehalose in neurodegenerative disorders. In the majority of reviewed studies, trehalose upregulates autophagy and improves physiological and behavioral symptoms in rodent models of neurodegeneration.

Zaltzman et al, 2020

Trehalose was well tolerated, and no serious drug-related adverse events were recorder in patients with Machado-Jospeh Disease. Functional scores for all patients remained stable at 6 months. Six patients received treatment for as long as 12 months and continued to remain stable on all the above tests.

Rusmini et al, 2019

Trehalose promotes autophagy via the activation of TFEB (transcription factor EB), which is important in ameliorating disease phenotypes in multiple neurodegenerative disease models. It regulates autophagy by inducing lysosomal enlargement and membrane permeabilization, which correlates with calcium-dependent phosphatase activation, TFEB dephosphorylation, and nuclear translocation. This process leads to the upregulation of genes related to lysosomal hydrolases, membrane proteins, and several autophagy-related components in a TFEB-dependent manner.

Noorasyikin et al, 2020

This study shows that oral trehalose is safe and was able to improve disease severity scores (SARA), 8-min walking test scores, and quality of life scores, in approximately 61% of SCA 3 patients at 6 months.

Cicardi et al, 2019

The study finds that the heat shock protein B8 (HspB8) aids in the autophagic removal of misfolded ARpolyQ, suggesting that treatments boosting autophagic flux and ARpolyQ clearance could be beneficial for SBMA patients. This publication shows that trehalose elevates Hspb8 mRNA levels.