Evoked Potentials and EEG Analysis in Rett Syndrome and Related Developmental Encephalopathies: Towards a Biomarker for Translational Research.

Joni N Saby,Sarika U Peters,Timothy P L Roberts,Eric D Marsh,Charles A Nelson

doi:10.3389/fnint.2020.00030

Abstract

Rett syndrome is a debilitating neurodevelopmental disorder for which no disease-modifying treatment is available. Fortunately, advances in our understanding of the genetics and pathophysiology of Rett syndrome has led to the development of promising new therapeutics for the condition. Several of these therapeutics are currently being tested in clinical trials with others likely to progress to clinical trials in the coming years. The failure of recent clinical trials for Rett syndrome and other neurodevelopmental disorders has highlighted the need for electrophysiological or other objective biological markers of treatment response to support the success of clinical trials moving forward. The purpose of this review is to describe the existing studies of electroencephalography (EEG) and evoked potentials (EPs) in Rett syndrome and discuss the open questions that must be addressed before the field can adopt these measures as surrogate endpoints in clinical trials. In addition to summarizing the human work on Rett syndrome, we also describe relevant studies with animal models and the limited research that has been carried out on Rett-related disorders, particularly methyl-CpG binding protein 2 (MECP2) duplication syndrome, CDKL5 deficiency disorder, and FOXG1 disorder.

Highlights

Rett syndrome is a genetic neurodevelopmental disorder that affects predominantly females
methyl-CpG binding protein 2 (MECP2) duplication syndrome, CDKL5 deficiency disorder (CDD), and FOXG1 disorder are severe neurodevelopmental conditions that result in life-long impairment across multiple domains of functioning
Promising therapeutics are being investigated in animal models, with many of these treatments likely to proceed to clinical trials in the coming years

Summary

Introduction

Rett syndrome is a genetic neurodevelopmental disorder that affects predominantly females. Advances in the understanding of the underlying pathophysiology have led to the development of new therapies, namely symptomatic pharmacologic interventions that act on the downstream cellular pathways affected in Rett syndrome, as well as gene therapy approaches that target the MECP2 gene directly. The effectiveness of these treatments in animal models of Rett syndrome has created enthusiasm within the Rett community as well as hope for a cure for the condition (van Karnebeek et al, 2016; Clarke and Abdala Sheikh, 2018). Despite the efficacy of these treatments at the preclinical level all of the treatments that have preceded to clinical trials have so far failed to show the anticipated effects (Glaze et al, 2009, 2017; Khwaja et al, 2014; O’Leary et al, 2018)

Objectives

Results

Discussion

Conclusion