CommentaryN-Methyl-D-Aspartate Receptors, Ketamine, and Rett Syndrome: Something Special on the Road to Treatments?
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Acknowledgments and Disclosures
David Katz’s laboratory is supported by grants from the National Institutes of Health (Grant No. NS087132), Rett Syndrome Research Trust, and AstraZeneca.
David Katz serves on the Scientific Advisory Board of the Rett Syndrome Research Trust, has been a consultant for SAGE Therapeutics during the past year, and is a founding advisor to ArRETT Neurosciences, a company seeking to develop treatments for Rett syndrome. Frank Menniti is founder, former Chief Scientific Officer, and stockholder of
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Cited by (18)
Breathing disturbances in Rett syndrome
2022, Handbook of Clinical NeurologyCitation Excerpt :A natural history study has provided deep insights into the Rett Syndrome classification and the various clinical phenotypes (Neul et al., 2014; Kaufmann et al., 2016; Katz et al., 2016a; Tarquinio et al., 2017, 2018; Buchanan et al., 2019; Stallworth et al., 2019). Unfortunately, despite major scientific breakthroughs, most clinical trials have failed, and the currently available therapies offer only very limited success (Percy, 1946; Leoncini et al., 2011; Pozzo-Miller et al., 2015; Katz et al., 2016a, 2016b; Nissenkorn et al., 2017; Smith-Hicks et al., 2017; MacKay et al., 2018; Singh and Santosh, 2018; Gomathi et al., 2020). Thus, the devastating breathing abnormalities, like most other symptoms, are largely resistant to pharmacological treatment.
Proteomic and transcriptional changes associated with MeCP2 dysfunction reveal nodes for therapeutic intervention in Rett syndrome
2021, Neurochemistry InternationalCitation Excerpt :Treatment of Mecp2-mutant mice with recombinant IGF1 protein reverses behavioral and synaptic defects (Castro et al., 2014; Tropea et al., 2009). This, combined with promising in vitro data showing beneficial effects of IGF1 in RTT patient iPSc-derived neurons (de Souza et al., 2017; Williams et al., 2014) has led to numerous clinical trials targeting IGF1 (Katz et al., 2016; O'Leary et al., 2018). As one example, recombinant human IGF1 (Mecasermin) treatment correlated with marked improvements in disease severity, social and cognitive measures in RTT patients versus untreated patients (Pini et al., 2016).
Rett Syndrome: A Timely Review From Recognition to Current Clinical Approaches and Clinical Study Updates
2021, Seminars in Pediatric NeurologyCitation Excerpt :Ketamine, a N-methyl-D-aspartate receptor antagonist, is a widely used anesthetic drug. Multiple animal related studies have shown that treatment with Ketamine ameliorated the apneic breathing and motor dysfunction in Mecp2-null mice.77,78 In 2019, a phase 2 randomized, double-blind, placebo controlled, cross-over study to assess the safety, tolerability, and efficacy of oral Ketamine for patients with Rett syndrome was initiated.
Rett syndrome and MECP2-related disorders
2020, Neurodevelopmental Disorders: Comprehensive Developmental NeuroscienceANAVEX®2-73 (blarcamesine), a Sigma-1 receptor agonist, ameliorates neurologic impairments in a mouse model of Rett syndrome
2019, Pharmacology Biochemistry and BehaviorCitation Excerpt :To date, no drug treatment has shown effectiveness in pivotal trials and, consequently, new pharmacological strategies are needed. Most of the clinical translational research in RTT has been based on compounds targeting the Insulin-like Growth Factor 1 (IGF-1) pathway, although treatments focused on specific circuits and neurotransmitters are also under investigation (Katz et al., 2016; Kaufmann et al., 2016; O'Leary et al., 2018; Glaze et al., 2019). Drugs that can restore cellular homeostasis and promote intrinsic compensatory synaptic mechanisms (Banerjee et al., 2019) are attractive candidates in RTT, particularly if they have already demonstrated promise in other neurologic disorders (Campbell et al., 2019; Grünewald et al., 2019; Tong et al., 2018; Jha et al., 2019).