Cardiorespiratory challenges in Rett's syndrome

Julu, Peter O.O.; Engerström, Ingegerd Witt; Hansen, Stig; Apartopoulos, Flora; Engerström, Bengt; Pini, Giorgio; Delamont, Robert S.; Smeets, Eric

doi:10.1016/s0140-6736(08)60849-1

Cited by 59 publications

(46 citation statements)

References 7 publications

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“…Several reasons could explain the lack of clinically significant effects of DMI on breathing patterns in RTT girls. First, as described by several authors, breathing dysfunction in RTT is very complex and highly variable 5, 6, 7, 8, 22. We monitored the breathing disorders in awake patients at each visit and found similar results on AHI to those reported in two patients with atypical Rett 23.…”

Section: Discussionsupporting

confidence: 57%

“…Among the symptoms of RTT, breathing dysrhythmia may represent a life‐threatening event 3. Breathing disorders are present in 65 to 93% of the patients and characterized by hyperventilation, hypoventilation, breath holds and apneic events 4, 5, 6, 7, 8. Studies in validated mouse models of RTT have shown that Mecp2 null male and heterozygous female mice exhibited breathing disturbances with different level of severity 9, 10, 11.…”

Section: Introductionmentioning

confidence: 99%

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Effect of desipramine on patients with breathing disorders in RETT syndrome

Mancini

Dubus

Jouve

et al. 2017

Ann Clin Transl Neurol

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ObjectiveRett Syndrome (RTT) is a severe neurodevelopmental condition with breathing disorders, affecting around one in 10,000 female births. Desipramine, a noradrenaline reuptake inhibitor, reduced the number of apneas in Mecp2‐deficient mice, a model of RTT. We planned a phase 2 trial to test its efficacy and its safety on breathing patterns in 36 girls with RTT.MethodsThe trial was a 6‐month, multicenter, randomized, double‐blind, placebo‐controlled study registered with ClinicalTrials.gov, number NCT00990691. Girls diagnosed according to clinical examination and confirmed by genotyping were randomly assigned in a 1:1:1 ratio to receive 2–3 mg/kg Desipramine per day (high Desipramine), 1–2 mg/kg Desipramine per day (low Desipramine), or a placebo. The primary outcome was the change of apnea hypopnea index (AHI), defined by the number of apnea and hypopnea events per hour, assessed at 6 months from baseline. Intention‐to‐treat analysis was applied.ResultsThe median change in AHI from baseline to 6 months was −31 (IQR: −37 to −11) for the high Desipramine, −17.5 (IQR: −31 to 13) for the low Desipramine, and −13 (IQR:−31 to 0) for the placebo group. We did not find any significant difference in these changes between the groups (P = 0.781). A significant inverse correlation between Desipramine plasma concentration and AHI (r = −0.44; P = 0.0002) was underlined.InterpretationThis first clinical trial of desipramine did not show clinical efficacy. Although required further studies, the significant correlation between Desipramine concentrations and improvement of AHI provided additional and relevant reasons to test the noradrenergic pathway in RTT.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Effect of desipramine on patients with breathing disorders in RETT syndrome

Mancini

Dubus

Jouve

et al. 2017

Ann Clin Transl Neurol

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“…Abnormal breathing, another symptom of RTT (19,33), was also impacted by the treatment. The change in mean breaths per minute was calculated to assess breathing variability (Fig.…”

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confidence: 99%

Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice

Tropea

Giacometti

Wilson

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

529

442

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“…3 Those affected have considerable difficulties in performing functional daily activities, particularly in relation to communication, 4 gross motorskills 5 and hand function. 6 Co-morbidities include poor growth, 7 breathing abnormalities, 8 scoliosis 9 , epilepsy 10 and sleep difficulties. 11 Overall, the clinical presentation is severe in terms of both functional impairment and associated medical problems.…”

Section: Introductionmentioning

confidence: 99%