Diabetes drug may help symptoms of autism-associated condition
Metformin, the most widely used drug to treat type听2 diabetes, could potentially be used to treat symptoms of Fragile X syndrome, an inherited form of intellectual disability and a cause of some forms of autism.
A new study led by researchers at 不良研究所, the University of Edinburgh and Universit茅 de Montr茅al has found that metformin improves social, behavioural and morphological defects in Fragile X mice.
Fragile X syndrome is a genetic disease caused by defects in the Fragile X Mental Retardation听1 gene (FMR1), which triggers excess production of protein in the brain, as well as dysregulated connections between neurons and changes in behaviour. The condition leads to impairments in speech and language, behaviour and social interaction. It affects about 1 in 5,000 boys and 1 in 6,000 girls and is often co-diagnosed with autism, anxiety disorders and seizures.
Fragile X mice 鈥� animals that display symptoms associated with the disease such as increased grooming and decreased socialization 鈥� showed normal brain connections and behavioural patterns after 10 days of injection with metformin.
Nahum Sonenberg, James 不良研究所 Professor at 不良研究所鈥檚 Biochemistry Department and co-senior author of the new study published in , said the findings offer hope for patients with Fragile X syndrome. 鈥淭his is some of the most exciting research work in my career, as it offers great promise in treating a pernicious genetic disease for which there is no cure,鈥� he said.
Christos Gkogkas, Chancellor鈥檚 Fellow at the University of Edinburgh鈥檚 Patrick Wild Centre explained that 鈥渕etformin has been extensively used as a therapy for type听2 diabetes for more than 30 years, and its safety and tolerability are well documented.鈥�
鈥淭his makes the drug an ideal candidate for fast-tracked clinical trials and, if all goes well, a readily available drug for the treatment of Fragile X syndrome,鈥� added Jean-Claude Lacaille, Canada Research Chair in Cellular and Molecular Neurophysiology and professor in the Department of Neurosciences at Universit茅 de Montr茅al and a major collaborator on the study.
'Wonder drug'
In the past few years, metformin has generated extensive interest for its potential in treating numerous health problems such as cancer, cardiovascular diseases, neurological diseases and aging.
鈥淏asically, it鈥檚 something like a wonder drug,鈥� Sonenberg said.
The study suggests that metformin might also be used to treat other autism spectrum disorders, said Ilse Gantois, a research associate in Sonenberg鈥檚 lab at 不良研究所.
鈥淲e mostly looked at the autistic form of behaviour in the Fragile X mouse model,鈥� explained Gantois, who is co-lead author with 不良研究所 researchers Arkady Khoutorsky and Jelena Popic. 鈥淲e want to start testing other mouse models to see if the drug could also have benefits for other types of autism.鈥�
The study also established that metformin restores some of the molecular pathways disrupted in the absence of the FMR1. The next step will be to understand the drug鈥檚 exact role in these pathways.
鈥淚t is a simple story in terms of the description of the corrections allowed by the drug,鈥� Sonenberg said. 鈥淲hat is more complicated is the molecular mechanism, how exactly it works. We need to study, in the lab, what molecules metformin interacts with and what cellular functions are affected.鈥�
Moreover, the drug could be tweaked 鈥渢o be more efficient than metformin鈥� and repurposed, for example, for other disorders, he added.
Funding was provided by the FRAXA Research Foundation, Brain Canada/FNC, a CIHR foundation grant (FDN-148423) and Brain & Behaviour Research Foundation grants to N.S.; a Wellcome Trust / Royal Society Sir Henry Dale grant (107687/Z/15/Z) to C.G.G.; the Canada Research Chair Program (950-231066) to J.-C.L.; and a Brain Canada/NeuroDevNet Postdoctoral Training Award to J.P.
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, by Ilse Gantois et al., Nature Medicine
