Oral treatment with desipramine improves breathing and life span in Rett syndrome mouse model.
Rett syndrome is a neurodevelopmental disease due to Mecp2 gene mutations that is associated to complex neurological symptoms, with bioaminergic deficits and life-threatening apneas related to sudden and unexpected death. In male mice, Mecp2-deficiency similarly induces medullary bioaminergic deficits, severe apneas and short life span. Here, we show that long-term oral treatment of Mecp2-deficient male mice with desipramine, an old drug of clinical use known to block norepinephrine uptake and to strengthen its synaptic effects, significantly alleviates their breathing symptoms and prolongs their life span. Although these mouse results identify desipramine as the first oral pharmacological treatment potentially able to alleviate breathing symptoms of Rett syndrome, we recommend further studies of desipramine effects in Mecp2-deficient mice before attempting any clinical trials in Rett patients.
Zanella
Sébastien
S
MP3-Respiration, UMR CNRS 6153, 280 Boulevard Sainte Marguerite, 13009 Marseille, France.
Mebarek
Saida
S
Lajard
Anne-Marie
AM
Picard
Nathalie
N
Dutschmann
Mathias
M
Hilaire
Gérard
G
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D001049:Apnea / Q000503:physiopathology; D003891:Desipramine / Q000627:therapeutic use*; D005260:Female; D008124:Locomotion / Q000187:drug effects; D008136:Longevity / Q000187:drug effects*; D008526:Medulla Oblongata / Q000378:metabolism; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008831:Microcephaly / Q000235:genetics / Q000517:prevention & control; D009638:Norepinephrine / Q000378:metabolism; D010991:Plethysmography; D015656:Respiratory Mechanics / Q000187:drug effects*; D015518:Rett Syndrome / Q000188:drug therapy* / Q000503:physiopathology
D000929:Antidepressive Agents, Tricyclic; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D003891:Desipramine; D009638:Norepinephrine