Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome
| Autor: | Florian Von Raison, Randall L. Carpenter, Will Spooren, George Apostol, Jacqueline N. Crawley, Eva Loth, Elizabeth Berry-Kravis, Lothar Lindemann, Vincent des Portes, Farah Hossain, Mark F. Bear, Randi J Hagerman, Sebastian H. Scharf, Baltazar Gomez-Mancilla, Paul P. Wang, David R Hessl, Sébastien Jacquemont, Fabrizio Gasparini, Aia E. Jønch, Aurore Curie |
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| Přispěvatelé: | Picower Institute for Learning and Memory |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Autism Drug Evaluation Preclinical Review Medical and Health Sciences 0302 clinical medicine Neurodevelopmental disorder Drug Discovery Intellectual disability 2.1 Biological and endogenous factors Pharmacology & Pharmacy Aetiology Randomized Controlled Trials as Topic Pediatric Clinical Trials as Topic Neurotransmitter Agents Metabotropic glutamate receptor 5 General Medicine Biological Sciences Preclinical Fragile X syndrome Mental Health Drug development 5.1 Pharmaceuticals Neurological Development of treatments and therapeutic interventions congenital hereditary and neonatal diseases and abnormalities Intellectual and Developmental Disabilities (IDD) Clinical Trials and Supportive Activities Article 03 medical and health sciences Rare Diseases Drug Development Clinical Research Behavioral and Social Science Journal Article medicine Animals Humans Pharmacology business.industry Neurosciences medicine.disease FMR1 Brain Disorders Clinical trial Orphan Drug 030104 developmental biology Neurodevelopmental Disorders Fragile X Syndrome Drug Evaluation business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Other repository Berry-Kravis, E M, Lindemann, L, Jønch, A E, Apostol, G, Bear, M F, Carpenter, R L, Crawley, J N, Curie, A, Des Portes, V, Hossain, F, Gasparini, F, Gomez-Mancilla, B, Hessl, D, Loth, E, Scharf, S H, Wang, P P, Von Raison, F, Hagerman, R, Spooren, W & Jacquemont, S 2018, ' Drug development for neurodevelopmental disorders : lessons learned from fragile X syndrome ', Nature Reviews. Drug Discovery, vol. 17, no. 4, pp. 280–299 . https://doi.org/10.1038/nrd.2017.221 Nature reviews. Drug discovery, vol 17, iss 4 |
| ISSN: | 1474-1784 1474-1776 |
| DOI: | 10.1038/nrd.2017.221 |
| Popis: | Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong cognitive and behavioural deficits and represent a major public health burden. FXS is the most frequent monogenic form of intellectual disability and autism, and the underlying pathophysiology linked to its causal gene, FMR1, has been the focus of intense research. Key alterations in synaptic function thought to underlie this neurodevelopmental disorder have been characterized and rescued in animal models of FXS using genetic and pharmacological approaches. These robust preclinical findings have led to the implementation of the most comprehensive drug development programme undertaken thus far for a genetically defined neurodevelopmental disorder, including phase IIb trials of metabotropic glutamate receptor 5 (mGluR5) antagonists and a phase III trial of a GABAB receptor agonist. However, none of the trials has been able to unambiguously demonstrate efficacy, and they have also highlighted the extent of the knowledge gaps in drug development for FXS and other neurodevelopmental disorders. In this Review, we examine potential issues in the previous studies and future directions for preclinical and clinical trials. FXS is at the forefront of efforts to develop drugs for neurodevelopmental disorders, and lessons learned in the process will also be important for such disorders. |
| Databáze: | OpenAIRE |
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