Abstract
Drug studies on Rett syndrome (RTT) have drastically increased over the past few decades. This review aims to provide master data on bench-to-bedside drug studies involving RTT. A comprehensive literature review was performed by searching in PUBMED, MEDLINE and Google Scholar, international, national and regional clinical trial registries and pharmaceutical companies using the keywords “Rett syndrome treatment and/or drug or compound or molecule”. Seventy drugs were investigated in non-clinical (N = 65 animal/cell line-based studies; N = 5 iPSC-based study) and clinical trials (N = 34) for ameliorating the symptoms of RTT. Though there is good progress in both clinical and non-clinical studies, none of these drugs entered phase III/IV for being launched as a therapeutic agent for RTT.
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Abbreviations
- RTT:
-
Rett syndrome
- MECP2 :
-
Human methyl CpG binding protein 2 gene
- Mecp2 :
-
Mouse methyl CpG binding protein 2
- MeCP2 :
-
Human methyl CpG binding protein 2
- CNS:
-
Central nervous system
- hiPSC:
-
Human induced pluripotent stem cell
- CDKL5 :
-
Cyclin-dependent kinase-like protein 5 gene
- HDAC :
-
Histone deacetylase
- QoL:
-
Quality of life
- CREB1 :
-
Cyclic adenine mono phosphate responsive element binding protein 1
- TrKB:
-
Tyrosine receptor kinase B
- DHF:
-
Dihydroxyflavone
- SNRI:
-
Selective norepinephrine reuptake inhibitor
- SSRI:
-
Selective serotonin reuptake inhibitor
- GABA:
-
Gamma-amino butyric acid
- PTP1B:
-
Protein tyrosine phosphate 1B
- CPT157633:
-
Difluoromethylphosphonic acid
- UA0713:
-
Ursolic acid derivative
- VPA:
-
Valproic acid
- NMDA:
-
N-methyl-d-aspartate
- KO:
-
Knock out
- BDNF:
-
Brain-derived neurotrophic factor
- 5-HT7R:
-
5-Hydroxytryptamine receptor 7
- BBB:
-
Blood brain barrier
- CNF-1:
-
Cytotoxic necrotizing factor 1
- IGF:
-
Insulin-like growth factor
- rhIGF:
-
Recombinant human insulin-like growth factor
- DCS:
-
d-Cycloserine
- F15599-3-Chloro-4:
-
Fluorophenyl-(4-fluoro-4-{[(5-methylpyrimidin-2-ylmethyl)-amino]-methyl}-piperidin-1-yl)-methanone
- 08-OH-DPAT :
-
8-Hydroxy-n,N-ipropylaminotetralin
- NO-711 :
-
1-[2-[[(diphenylmethylene)imino]oxy]ethyl]-1,2,5,6-Tetrahydro-3-pyridine-carboxylicacid-hydrochloride
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Acknowledgment
This work was supported by University Grants Commission—National Fellowship for Scheduled Caste Candidates Mrs. Gomathi, UGC—RGNF JRF (Award number and date: F1-17.1/2017-18/RGNF-2017-18-SC-TAM-35724 /(SA-III/Website) 02/08/2017) and also this study was supported by grants from the Science and Engineering Research Board (SERB) Early Career Research (ECR) Award funded by the Government of India, New Delhi (Grant No. ECR/2016/ 001688). We acknowledge the department of Human Genetics and Molecular Biology, Bharathiar University for providing necessary infrastructure facilities and technical assistance to conduct this article.
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MG conceived of the study, participated in its design and coordination and drafted the manuscript; SP participated in the design and interpretation of the data; VB participated in the design and coordination of the study and helped to draft the manuscript. All authors read and approved the final manuscript.
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Gomathi, M., Padmapriya, S. & Balachandar, V. Drug Studies on Rett Syndrome: From Bench to Bedside. J Autism Dev Disord 50, 2740–2764 (2020). https://doi.org/10.1007/s10803-020-04381-y
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DOI: https://doi.org/10.1007/s10803-020-04381-y