A Differential Effect Of Lovastatin Versus Simvastatin In Neurodevelopmental Disorders

The statin drug lovastatin normalizes excessive protein synthesis and thereby ameliorates pathological changes in animal models of Fragile X Syndrome (FX), the most commonly identified genetic cause of autism. Recently, we compared the efficacy of lovastatin to the more potent and brain-penetrant drug simvastatin for correcting phenotypes in the mouse (Muscas et al., 2019). Surprisingly, we find simvastatin worsens excessive protein synthesis and has no impact on audiogenic seizures (AGS) in mice, suggesting it does not work in a similar fashion to lovastatin. A recent commentary by Ottenhoff et al. suggests that differences in dose and/or study design might account for our results. Here we discuss the points raised by Ottenhoff et al., as well as the evidence supporting a therapeutic role for lovastatin versus simvastatin. We conclude that differences between lovastatin and simvastatin warrant careful consideration with respect to the treatment of neurodevelopmental disorders.