Experimental Therapy Appears to Improve Some Huntington’s Symptoms in Mouse Study

Joana Fernandes, PhD avatar

by Joana Fernandes, PhD |

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Despite efforts to develop therapies to treat Huntington’s disease (HD), so far no treatment has been shown to effectively stop, slow, or reverse disease progression. Now, an animal study suggests that treating mice with the experimental drug laquinimod can improve some neuropathologic and behavioral features of Huntington’s.

The study, titled “Laquinimod Rescues Striatal, Cortical and White Matter Pathology and Results in Modest Behavioral Improvements in the YAC128 Model of Huntington’s Disease,” was published in Scientific Reports.

Mice genetically modified to express the mutated form of the huntingtin protein (HTT) were treated with oral laquinimod daily for five days a week over six months. The dosage was of 1 mg/kg of laquinimod, or 10 mg/kg of laquinimod at a volume of 4 mL/kg, depending on the weight of the animals in the study.

The authors observed that the animals treated with laquinimod showed restored atrophy in the striatum, in certain cortical regions, and in the corpus callosum; had improved white matter microstructural abnormalities in the posterior corpus callosum; and showed reduced levels of the immune factor IL-6 in the periphery. Moreover, they also presented modest improvements in motor function and in depressive-like behavior.

Both doses were able to recover striatal volume in the animal, but only the low dose (1 mg/kg) improved white matter microstructural abnormalities and serum interleukin-6 (IL-6) levels (an indicator of immune system activation), and induced earlier and longer persisting improvements in motor function.

“These observations suggest that multiple, dose-sensitive mechanisms might be mediating the action of laquinimod,” the authors wrote in their report.

Laquinimod, a central nervous system-active immunomodulator, has been previously described as a brain-permeable agent with a regulatory effect on the immune system, primarily by modulating excessive NF-kB activation in Huntington’s disease. Therefore, the authors believe that “modulation of HD-related pathological immune activation, possibly through NF-kB modulation, may have contributed to the improved neuropathology and functional outcomes reported here.”

Despite the positive results, this study had some limitations, such as the impossibility to study the effects of laquinimod in cognitive dysfunction and anxiety symptoms in mice, and the fact that the treatment started before the onset of Huntington’s symptoms in these animals. In the future, it would be interesting to evaluate whether laquinimod can still have a beneficial effect when administered earlier or in advanced stages of the disease.