Respiratory problems, such as irregular breathing and apnea during resting and/or sleeping, are a common feature in patients with Rett syndrome (RTT). Three studies here outlined describe three different approaches to these problems and present encouraging results.

The first article describes the results obtained using a serotonin receptor agonist, whose commercial name is Sarizotan, in the treatment of respiratory (and locomotion) impairment in RTT mouse models. The breathing pattern was corrected to the same level of wild-type mice, while the apnea episodes showed a reduction.

The second article focuses on the brain-derived neurotrophic factor (BDNF) role, whose low levels are thought to contribute to the pathophysiology of the RTT. As in mice the reduction of the BDNF has been linked with a breathing impairment, a group of researchers tested the effects of a small molecule, called LM22A-4. This molecule mimics the effects of the BDNF and takes part in the excitability of the respiratory cells in the brainstem. RTT mice treated with LM22A-4 had the complete elimination of the apneas and the reversal of the respiratory dysregulation.

Finally, the third article describes the treatment of an 11-year-old RTT patient with frequent apneas during the sleep. The young girl, normally helped to breathe through a ventilation system, was treated with an inhibitor of the serotonin reuptake. The administration of such serotonergic agent reduced the sleep apneas even without the help of the ventilation system. So, the authors concluded that this class of molecules might improve the functionality of the inspiratory and expiratory neurons.



Find below the mentioned articles. The first two of them are freely available on the web.


Abdala A.P. et al., Effect of Sarizotan, a 5-HT1a and D2-like receptor agonist, on respiration in three mouse models of Rett syndrome. Am J Respir Cell Mol Biol. 2014 Jun;50(6):1031-9. doi: 10.1165/rcmb.2013-0372OC.


Kron M. et al., A BDNF loop-domain mimetic acutely reverses spontaneous apneas and respiratory abnormalities during behavioral arousal in a mouse model of Rett syndrome. Dis Model Mech. 2014 Sep;7(9):1047-55. doi: 10.1242/dmm.016030.


Ohno K. et al., Effect of Serotonin 1A Agonists and Selective Serotonin Reuptake Inhibitors on Behavioral and Nighttime Respiratory Symptoms in Rett Syndrome. Pediatr Neurol. 2016 Jul;60:54-59.e1. doi: 10.1016/j.pediatrneurol.2016.03.016. Epub 2016 Apr 1.




The elaboration of this post has been financed by the project PI15/01082, as a part of the National Plan of I+D+I and co-financed by the ISCIII – General Deputy Direction for Evaluation and Development of Health Research – and the European Regional Development Fund (ERDF).