In her FFG-funded PhD thesis in cooperation with Ludwig Aigner of the Paracelsus University, Salzburg, Austria, Katharina Strempfl currently investigates whether leukotriene inhibition can improve motor impairments in Line 61 mice. Katharina treated Line 61 and non-transgenic (ntg) littermates daily with an oral film (IntelGenx Technologies) containing Montelukast, a cysteinyl leukotriene receptor antagonist that is already approved for the treatment of asthma. Treatment started at an age of 2 weeks for a total of 10 weeks. The effects of Montelukast on motor abilities were assessed after 5 and 10 weeks.
Montelukast was able to improve motor coordination and balance as assessed by the beam walk test in Line 61 mice (Fig.1). The number of slips as well as the number of slips per speed of Line 61 mice was significantly decreased already after 5 weeks of Montelukast treatment (Fig. 1A+C). From treatment week 5 to 10, Montelukast significantly reduced the time that Line 61 animals needed to traverse the beam and in treatment week 10, Montelukast-treated Line 61 mice showed a significantly reduced active time than vehicle-treated Line 61 animals (Fig. 1B). Analysis of all animals in the wire suspension and grip strength test resulted in no significant differences between vehicle- and Montelukast-treated Line 61 mice (data not shown).
In conclusion, Montelukast affects and ameliorates motor coordination and balance. These findings suggest, that Montelukast is a suitable candidate to be repurposed as a treatment for motor impairments in synucleinopathies.
Figure 1: Beam walk test of vehicle- or Montelukast-treated ntg and Line 61 mice. The total number of slips (A), the time for traversing the beams in seconds (B) and the number of slips per speed (C) were assessed on a 13 mm wide square beam. n = 18-22 per group; mean + SEM; three-way ANOVA followed by Bonferroni’s multiple comparison post hoc test; *p<0.05, **p<0.01, **p<0.001.
Figure 2: Representative image of the hippocampal formation of a 3-months old Line 61 mouse. Tissue was labeled for 5-lipoxygenase (5-Lox; red) the rate-limiting enzyme of leukotriene synthesis and counterstained with DAPI to visualize nuclei.