|Treatment of a Mouse Model of Fragile X Syndrome with MPEP
By Linda Crnic, 1/1/2003
We are very interested in mGluR antagonists because of their potential as treatments for Fragile X. MPEP is an mGluR antagonist which specifically reduces activity of mGluR subtype 5 (known as mGluR5). Low doses of MPEP increase social exploration, decrease seizures, decrease anxiety, and decrease responses to stress in normal mice and rats. We injected Fragile X knockout mice with MPEP and measured their startle response to sound.We chose this test because many investigators have shown that Fragile X mice have an altered startle response to sound when compared to wildtype (normal) mice: they are more sensitive to low intensity sounds, normal in their response to intermediate sounds, and less sensitive to intense sounds. This may correspond to the altered sensory reactivity seen in individuals with Fragile X syndrome. Our studies show that effect of MPEP is confined to the intermediate loudnesses of the startle sound. Wildtype mice increased their response to the sound, while the knockouts decreased their response. We have just received funding from FRAXA to continue studies of MPEP. We will first explore other behaviors that might be affected by the drug and then determine the minimally effective dose. This dose will then be given on a regular basis, as this would be the likely clinical use of this or similar drugs. Finally, we will determine whether chronic use ameliorates symptoms of Fragile X syndrome without impairing cognitive function.