TY - JOUR
T1 - Rett Syndrome
T2 - Crossing the Threshold to Clinical Translation
AU - Katz, David M.
AU - Bird, Adrian
AU - Coenraads, Monica
AU - Gray, Steven J.
AU - Menon, Debashish U.
AU - Philpot, Benjamin D.
AU - Tarquinio, Daniel C.
N1 - Funding Information:
This work was supported by grants awarded to D.M.K. from NINDS (RO1NS057398) and the Rett Syndrome Research Trust (RSRT); to A.B. from The Wellcome Trust (grants 091580 and 092076) and RSRT; to B.D.P. from the Simons Foundation (SFARI Award 274426), NINDS (R01NS085093), NIMH (R01MH093372), and RSRT; to S.J.G. from Rettsyndrome.org, RSRT and Research to Prevent Blindness through the UNC Department of Ophthalmology; to D.U.M. from NICHD (RO1HD036655; T. Magnuson, PI). The authors thank Dr. James Eubanks for helpful discussions and Erica Kimmick for help with citations. Authorship: Authors’ names are listed in alphabetic order after D.M.K.
Funding Information:
This work was supported by grants awarded to D.M.K. from NINDS (RO1NS057398) and the Rett Syndrome Research Trust (RSRT); to A.B. from The Wellcome Trust (grants 091580 and 092076) and RSRT; to B.D.P. from the Simons Foundation (SFARI Award 274426), NINDS (R01NS085093), NIMH (R01MH093372), and RSRT; to S.J.G. from Rettsyndrome.org, RSRT and Research to Prevent Blindness through the UNC Department of Ophthalmology; to D.U.M. from NICHD (RO1HD036655; T. Magnuson, PI). The authors thank Dr. James Eubanks for helpful discussions and Erica Kimmick for help with citations. Authorship: Authors’ names are listed in alphabetic order after D.M.K.
Publisher Copyright:
© 2016.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Lying at the intersection between neurobiology and epigenetics, Rett syndrome (RTT) has garnered intense interest in recent years, not only from a broad range of academic scientists, but also from the pharmaceutical and biotechnology industries. In addition to the critical need for treatments for this devastating disorder, optimism for developing RTT treatments derives from a unique convergence of factors, including a known monogenic cause, reversibility of symptoms in preclinical models, a strong clinical research infrastructure highlighted by an NIH-funded natural history study and well-established clinics with significant patient populations. Here, we review recent advances in understanding the biology of RTT, particularly promising preclinical findings, lessons from past clinical trials, and critical elements of trial design for rare disorders.
AB - Lying at the intersection between neurobiology and epigenetics, Rett syndrome (RTT) has garnered intense interest in recent years, not only from a broad range of academic scientists, but also from the pharmaceutical and biotechnology industries. In addition to the critical need for treatments for this devastating disorder, optimism for developing RTT treatments derives from a unique convergence of factors, including a known monogenic cause, reversibility of symptoms in preclinical models, a strong clinical research infrastructure highlighted by an NIH-funded natural history study and well-established clinics with significant patient populations. Here, we review recent advances in understanding the biology of RTT, particularly promising preclinical findings, lessons from past clinical trials, and critical elements of trial design for rare disorders.
KW - Clinical trials
KW - Epigenetics
KW - Gene therapy
KW - MECP2
KW - Neurodevelopmental disorders
KW - Preclinical models
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U2 - 10.1016/j.tins.2015.12.008
DO - 10.1016/j.tins.2015.12.008
M3 - Review article
C2 - 26830113
AN - SCOPUS:84959056410
SN - 0166-2236
VL - 39
SP - 100
EP - 113
JO - Trends in Neurosciences
JF - Trends in Neurosciences
IS - 2
ER -