TY - JOUR
T1 - Neurobiologically-based treatments in Rett syndrome
T2 - opportunities and challenges
AU - Kaufmann, Walter E.
AU - Stallworth, Jennifer L.
AU - Everman, David B.
AU - Skinner, Steven A.
N1 - Funding Information:
The authors of this paper received grant support from the NIH [U54 HD061222] and from Rettsyndrome.org [2907 and 3105].
Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2016/10/2
Y1 - 2016/10/2
N2 - Introduction: Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that primarily affects females, typically resulting in a period of developmental regression in early childhood followed by stabilization and severe chronic cognitive, behavioral, and physical disability. No known treatment exists beyond symptomatic management, and while insights into the genetic cause, pathophysiology, neurobiology, and natural history of RTT have been gained, many challenges remain. Areas covered: Based on a comprehensive survey of the primary literature on RTT, this article describes and comments upon the general and unique features of the disorder, genetic and neurobiological bases of drug development, and the history of clinical trials in RTT, with an emphasis on drug trial design, outcome measures, and implementation. Expert opinion: Neurobiologically based drug trials are the ultimate goal in RTT, and due to the complexity and global nature of the disorder, drugs targeting both general mechanisms (e.g., growth factors) and specific systems (e.g., glutamate modulators) could be effective. Trial design should optimize data on safety and efficacy, but selection of outcome measures with adequate measurement properties, as well as innovative strategies, such as those enhancing synaptic plasticity and use of biomarkers, are essential for progress in RTT and other neurodevelopmental disorders.
AB - Introduction: Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that primarily affects females, typically resulting in a period of developmental regression in early childhood followed by stabilization and severe chronic cognitive, behavioral, and physical disability. No known treatment exists beyond symptomatic management, and while insights into the genetic cause, pathophysiology, neurobiology, and natural history of RTT have been gained, many challenges remain. Areas covered: Based on a comprehensive survey of the primary literature on RTT, this article describes and comments upon the general and unique features of the disorder, genetic and neurobiological bases of drug development, and the history of clinical trials in RTT, with an emphasis on drug trial design, outcome measures, and implementation. Expert opinion: Neurobiologically based drug trials are the ultimate goal in RTT, and due to the complexity and global nature of the disorder, drugs targeting both general mechanisms (e.g., growth factors) and specific systems (e.g., glutamate modulators) could be effective. Trial design should optimize data on safety and efficacy, but selection of outcome measures with adequate measurement properties, as well as innovative strategies, such as those enhancing synaptic plasticity and use of biomarkers, are essential for progress in RTT and other neurodevelopmental disorders.
KW - MECP2
KW - Rett syndrome (RTT)
KW - fragile X syndrome (FXS)
KW - outcome measure
UR - http://www.scopus.com/inward/record.url?scp=84988926382&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84988926382&partnerID=8YFLogxK
U2 - 10.1080/21678707.2016.1229181
DO - 10.1080/21678707.2016.1229181
M3 - Review article
C2 - 28163986
AN - SCOPUS:84988926382
VL - 4
SP - 1043
EP - 1055
JO - Expert Opinion on Orphan Drugs
JF - Expert Opinion on Orphan Drugs
SN - 2167-8707
IS - 10
ER -