Novel Friedreich’s Ataxia Mouse Model May Be Helpful to Assess Potential Future Therapies

A new study from the University of California reported several unknown neurobehavioral deficits observed in an animal model for Friedrich’s ataxia (FA) that can be used to assess the effect of potential drug therapies.

The study, “Neurobehavioral deficits in the KIKO mouse model of Friedreich’s ataxia,” was published by Marissa McMackin, PhD, and her colleagues in the journal Behavioural Brain Research.

To study these FA-related neurobehavioral deficits, researchers preformed several behavioral tests in the KIKO (knockin-knock-out) mice, a reliable FA animal model. The objective was to determine which tests would provide information on abnormalities induced by a deficiency in the frataxin protein (the cause for FA), and to assess whether these could be similar to the neurobehavioral deficits observed in patients.

Mice were subjected to tests intended to closely mimic the methods used in the evaluation of posture, gait, and ataxia parameters used in the diagnosis of FA patients.

“The KIKO mouse neurobehavioral phenotype … includes cerebellar ataxia, decreased peripheral sensitivity, and decreased motor strength and endurance,” the authors wrote in their report.

The results revealed that the tests provided translatable neurobehavioral deficits relevant to clinical manifestations observed in Friedreich’s ataxia patients. In particular, the animals presented significantly reduced grip time, which is indicative of reduced muscle strength and is compatible with altered hand function observed in FA patients. They also presented reduced endurance, which, considering that FA is a mitochondrial disease, may explain why patients have a decreased capability to sustain activity.

Researchers also detected a reduction in the peripheral sensitivity of the hind paws of the animals, which is comparable to the loss of tactile sensitivity in the lower limbs of FA patients as a result of the loss of dorsal root ganglion neurons and dorsal spinal cord nerve fibers.

Finally, KIKO mice presented signs of classical ataxia, such as a decrease in normal step sequence and a wider stance resulting from their reduced stability.

The authors believe that the description of these abnormalities supports KIKO mice as a reliable model for the study of Friedreich’s ataxia, and that these features can be used in future studies to follow neurodegenerative disease progression and the therapeutic benefit of potential drug therapies in this mouse model.