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Evaluating the effects of a possible therapeutic drug for Rett Syndrome in a mouse model

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Author(s)
Lam, Maxine
Advisor(s)
Chang, Qiang (Mentor)
Degree
BS
Date
2010
Subject(s)
Genetics
Abstract
Rett Syndrome (RTT) is a neurodevelopmental disorder that affects girls with an estimated prevalence of 1 in 10,000-15,000, with no current cure or effective treatment. Most RTT cases are caused by human methyl-CpG binding protein 2 gene (Mecp2) mutations. Brain-derived neurotrophic factor (Bdnf) is the only MeCP2 target gene whose role in RTT disease progression has been studied in vivo. In a RTT mouse model, mutant mice express less BDNF and overexpression of BDNF delays disease progression. However, BDNF has poor pharmacological potential as it cannot cross the blood-brain barrier (BBB). We thus thought to mimic BDNF using a small agonist, 7,8-dihydroxyflavone (DHF), which can pass the BBB. This study tested subcutaneous and oral treatment of DHF in Mecp2 null mice and found that it rescued lifespan, healthy weight gain and locomotor activity. Preliminary findings on respiratory activity also indicate an exaggerated response to hypoxia in Mecp2 null mice, suggesting a disturbance in the peripheral nervous system breathing response.
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12 p.
Permanent link
http://digital.library.wisc.edu/1793/46038 
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