Short-term treatment early in life with lovastatin, a medication widely prescribed for lowering cholesterol, can rescue memory deficits in a rat model of fragile X syndrome, a study shows.
The study, “Sustained correction of associative learning deficits after brief, early treatment in a rat model of Fragile X syndrome,” was published in the journal Science Translational Medicine.
Previous research in preclinical models of fragile X has shown that treatment with certain medicines — such as lovastatin (sold under the brand names Altocor, Altoprev, Mevacor) — corrected brain deficits linked with the disease.
However, a “key question for the potential treatment of [fragile X] is the age at which treatment should begin to maximize effectiveness,” the researchers wrote.
Prior research has shown that lovastatin, when given continuously, is able to correct abnormal behaviours, such as hyperactivity and other disease symptoms. However, it’s unknown whether the treatment has therapeutic benefits when given for a transient period shortly after birth.
Therefore, researchers at the University of Edinburgh used a rat model of fragile X, engineered to lack the FMR1 gene — which encodes for the FMRP protein and, when mutated, is responsible for the disease.
Compared with wild-type (control) rats, fragile X rats showed a cognitive developmental delay and were no longer capable of discriminating between novel and familiar objects.
The team treated a group of rats with lovastatin for five weeks given between the age of 5 and 9 weeks — the time period when these animals were developing these memory abilities. Rats received lovastatin orally, mixed with their food. Animals fed without lovastatin were used as controls.
Results showed that lovastatin given for five weeks restored memory development in these animals. Furthermore, the rats still had the ability to complete specific memory tasks after more than three months following the end of treatment, suggesting the treatment’s effects were long-lasting.
Transient treatment with lovastatin normalized excessive protein production in the brain (known to occur as a result of FMRP loss), specifically in the hippocampus — a brain area key to memory, learning, and emotions — and prevented additional neuronal defects.
Children with fragile X are typically diagnosed at approximately three years of age, although genetic tests have allowed earlier diagnosis, which may enable treatments to be initiated earlier. The study’s results suggest that treating children with statins — the family of medicines that include lovastatin — may have beneficial effects if started early in life.
“We have found that early intervention for a limited period during development can lead to persistent beneficial effects, long after treatment ends, in a rat model of Fragile X Syndrome. Our future experiments will focus on whether there is a critical time-window during development when treatment is more effective,” Peter Kind, PhD, director of the Patrick Wild Centre and Simons Initiative for the Developing Brain at the University of Edinburgh and the study’s co-lead author said in a press release.
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