President Berger-Sweeney & Rett Syndrome

Tommy Hum-Hyder

In her talk entitled, Of Mice and Men and Girls and Autism, President Berger-Sweeney reviewed her years of research looking at the relationship of the MeCP2 transcriptional regulatory protein on a mouse model of Rett Syndrome (Katz et al., 2012). The crux of her research was focused on the 1 in 10,000 females, who are born with this regressive developmental disorder. For the first 6-18 months post-natal, the child appears to develop normally; subsequently, muscle begins to atrophy, difficulty crawling or walking, as well as Autism Spectrum Disorder (ASD) type symptoms, such as reduced eye contact. (NINDS, 2015).

Prior to President Berger-Sweeney’s research, scientists believed that the cognitive and behavioral abnormalities associated with Rett Syndrome were due to deficits in the cholinergic system, which they believed was due to abnormalities in the MeCP2 protein, a transcriptional repressor protein. Berger-Sweeney and team decided to proceed with a mouse model despite many colleagues in other research fields using rat models. President Berger-Sweeney spoke of the importance of a good animal model and of the first questions that her research group asked, which included whether to model symptoms, genetics, neurochemical changes, or neuroanatomical changes. The group decided to proceed with a mouse model with MeCP2 gene knockouts.

After many years of research, the group found that the male mice with the gene knockout made to replicate Rett Syndrome experienced an increased in social behavior, which, at first, seemed to contradict typical Rett Syndrome symptoms. However, a literature review suggested that it is possible for Rett Syndrome human females to have increased social behavior, suggesting that the mouse model could be a good measure. The group then decided to look at ways in which they could take this effective genetic mouse model and try to improve symptoms. They began by using choline, a precursor molecule of the neurotransmitter acetylcholine. At muscle junctions, acetylcholine facilitates muscle contractions. Research has also suggested that it may be involved with awareness and attention, which could address cognitive Rett Syndrome symptoms. After positive results, the group decided to use an acetylated version of the l-carnitine molecule called acetyl-l-carnitine, which they gave to mice as a nutritional supplement. They then improved results relative to the choline treatments, but results also showed that the improvement only lasted until 30 days postnatal. This would lead to inconclusive results relevant to the treatment of Rett Syndrome in humans; however, due to few researchers interested in Rett Syndrome, any progress towards the eventual amelioration of symptoms can be considered a great advance in the study of females with Rett Syndrome.

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