Reversal of behavioural phenotype by the cannabinoid-like compound VSN16R in fragile X syndrome mice.
Brain
; 145(1): 76-82, 2022 03 29.
Article
em En
| MEDLINE
| ID: mdl-34196695
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 causes 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 patients with multiple sclerosis with high oral bioavailability and no serious adverse effects reported. VSN16R could therefore be directly utilized 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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Canabinoides
/
Transtorno do Espectro Autista
/
Síndrome do Cromossomo X Frágil
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Brain
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Reino Unido