Huntington’s Disease: A Sweet New Treatment

Abstract & Commentary

Source: Tanaka M, et al. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington’s disease. Nature Med. 2004;10:148-154.

Huntington’s disease is a progressive neurodegenerative disease with onset generally in midlife. Insoluble huntingtin protein aggregates have been seen in vitro in mammalian cells, as well as in transgenic mouse models and in brain tissues from patients with Huntington’s disease. The relationship between the presence of the insoluble protein aggregates and Huntington’s disease pathogenesis has been controversial. A major focus of research, however, has been to screen for inhibitors of polyglutamine aggregation. Tanaka and associates used in vitro screening of a number of various disaccharides to determine whether they can inhibit polyglutamine-mediated protein aggregation. They found that several disaccharides reduced polyglutamine aggregates and increased survival in a cellular model of Huntington’s disease. These compounds were also effective in inhibiting aggregation in vitro. They then administered trehalose orally to a transgenic mouse model of Huntington’s disease. Trehalose was most effective of the disaccharides. It decreased polyglutamine aggregates in both the brain and the liver, improved motor function, and extended lifespan. The dilation of the ventricles seen in the Huntington’s disease model was significantly reduced. Mice improved motor performance on the rotarod and in foot-printing tests.


The present results are of interest since they suggest a new potential therapy for Huntington’s disease. The effects of trehalose appear to be due to binding directly to proteins with expanded polyglutamines. The lack of toxicity and high solubility coupled with efficacy of oral administration make trehalose a promising therapeutic drug or lead compound for the treatment of polyglutamine diseases. The magnitude of the increase in survival was approximately 10%, which is not as great as some other therapeutic interventions. Nevertheless, trehalose and other disaccharides may lead to important new therapies for Huntington’s disease. — M. Flint Beal

Dr. Beal, Professor and Chairman; Department of Neurology; Cornell University Medical College New York, NY is Editor of Neurology Alert.