Rare Disease Report

Can a Ganglioside Stop Huntington's Disease

OCTOBER 12, 2017
James Radke
An interesting and potentially game-changing animal study was published in EMBO Molecular Medicine recently, and it could lead to a viable treatment for patients with Huntington’s disease (HD).

HD is is a progressive neurodegenerative genetic disorder characterized by a combination of motor, cognitive and psychiatric problems that usually present in a person’s 3rd or 4th decade of life. Current treatment options are limited to relieving symptoms, but at present, there is no treatment to prevent or attenuate the disease’s progression.

Melanie Alpaugh and colleagues at the University of Alberta in Edmonton, Canada have conducted a series of tests that exhibit the improvement and occasional reversal of symptoms I mice models of HD with the administration of ganglioside GM1 (monosialotetrahexosylganglioside).

Gangiosides are glycosphingolipid with one or more sialic acids that are involved in a number of cellular processes. Animals without gangliosides display numerous neurological impairments (motor function loss, depression-lie behaviorl, congnitive impairment) and the University of Alberta researchers hypothesized that the addition of GM1 may improve some of the symptoms on display in HD.

The study found that intracerebroventricular infusion of GM1 slows down neurodegeneration, improves neuropathology and decreases body weight loss in R6/2 mice, 1 of 3 HD models used in the study. More specifically, the researchers observed that administration of GM1 significantly increased the number of neurons in the striatum as well as increasing total brain volume and brain weight. Other biomarkers of neuropathology were also reduced in the mice given GM1.

In a second HD model involving Q140 mice, detailed assessment of the neuropathology within the basal ganglia showed the administration to attenuate HD neurodegeneration.

Most importantly, treatment with GM1 led to a reduction in the mutant huntingtin protein in striatal tissue samples.

Treatment with GM1 improves motor performance in R6/2 and Q140 mice using a variety of tests, including horizontal ladder tests, open field activity tests, climbing tests, speed tests, and numerous gait abnormality tests. Furthermore, Q140 mice and a third HD model, YAC128, showed that GM1 also improved anxiety-like and depression-like behaviors (i.e.m novelty-supressed feeding, spontaneous fecal excretion, forced swim test, time in dark areas of cage).

The researchers concluded their report by stating: “To the best of our knowledge, the widespread therapeutic and disease‐modifying effects of GM1 observed in our studies are only comparable to (and even exceed in certain cases) those exerted by antisense oligonucleotide therapies to decrease HTT production.”

The numerous physical, chemical, and behavoural changes that appear to be attenuated by the administration of GM1 in these HD animal models warrants further investigation.
Arpaugh M, Galleguillos D, Forero J, et al. Disease‐modifying effects of ganglioside GM1 in Huntington's disease models. EMBO Mol Med. Published online October 9, 2017,  DOI 10.15252/emmm.201707763

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