dc.contributor.author | Hurley, MJ | |
dc.contributor.author | Deacon, RMJ | |
dc.contributor.author | Chan, AWE | |
dc.contributor.author | Baker, D | |
dc.contributor.author | Selwood, DL | |
dc.contributor.author | Cogram, P | |
dc.date.accessioned | 2021-08-09T11:20:33Z | |
dc.date.available | 2021-06-06 | |
dc.date.available | 2021-08-09T11:20:33Z | |
dc.date.issued | 2021-07-01 | |
dc.identifier.citation | Michael J Hurley, Robert M J Deacon, A W Edith Chan, David Baker, David L Selwood, Patricia Cogram, Reversal of behavioural phenotype by the cannabinoid-like compound VSN16R in fragile X syndrome mice, Brain, 2021;, awab246, https://doi.org/10.1093/brain/awab246 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/73519 | |
dc.description.abstract | Fragile X Syndrome is the most common inherited intellectual disability and mono-genetic cause of autism spectrum disorder. It is a neurodevelopmental condition occurring due to a CGG trinucleotide expansion in the FMR1 gene. Polymorphisms and variants in large-conductance calcium-activated potassium channels are increasingly linked to intellectual disability and loss of FMR protein caused reduced large-conductance calcium-activated potassium channel activity leading to abnormalities in synapse function. Using the cannabinoid-like large-conductance calcium-activated potassium channel activator VSN16R we rescued behavioural deficits such as repetitive behaviour, hippocampal dependent tests of daily living, hyperactivity and memory in a mouse model of fragile X syndrome. VSN16R has been shown to be safe in a phase 1 study in healthy volunteers and in a phase 2 study in people with Multiple Sclerosis with high oral bioavailability and no serious adverse effects reported. VSN16R could therefore be directly utilised in a fragile X syndrome clinical study. Moreover, VSN16R showed no evidence of tolerance, which strongly suggests that chronic VSN16R may have great therapeutic value for fragile X syndrome and autism spectrum disorder. This study provides new insight into the pathophysiology of fragile X syndrome and identifies a new pathway for drug intervention for this debilitating disorder. | en_US |
dc.language | eng | |
dc.relation.ispartof | Brain | |
dc.rights | This is a pre-copyedited, author-produced version of an article accepted for publication in Brain following peer-review. The version of record: Michael J Hurley, Robert M J Deacon, A W Edith Chan, David Baker, David L Selwood, Patricia Cogram, Reversal of behavioural phenotype by the cannabinoid-like compound VSN16R in fragile X syndrome mice, Brain, 2021;, awab246, https://doi.org/10.1093/brain/awab246 is available online at: https://doi.org/10.1093/brain/awab246 | |
dc.subject | BK channel | en_US |
dc.subject | FMRP | en_US |
dc.subject | Fmr1 knockout mouse | en_US |
dc.subject | VSN16R | en_US |
dc.subject | fragile X syndrome | en_US |
dc.title | Reversal of behavioural phenotype by the cannabinoid-like compound VSN16R in fragile X syndrome mice. | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1093/brain/awab246 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/34196695 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
dcterms.dateAccepted | 2021-06-06 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |