A new animal study has highlighted the possible benefits of CBD and the diabetes drug, metformin, for treating behavioural difficulties.
According to research presented at the Federation of European Neuroscience Societies (FENS) Forum 2024, studies of mouse models of Fragile X syndrome and Phelan-McDermid syndrome show that treatment with cannabidiol (CBD) and the diabetes drug metformin can alleviate behavioural difficulties.
Fragile X syndrome and Phelan-McDermid syndrome are two genetic conditions that cause a variety of neurodevelopmental difficulties throughout life.
Both conditions have a high incidence of autism spectrum disorder, including speech delay, social difficulties and repetitive behaviour.
The research was presented by Dr Ilse Gantois from McGill University, Montreal, Canada, who explained: “There are several drugs used to treat depression, anxiety, epilepsy and aggression in people with Fragile X. Most of these drugs have many side effects. Similarly, for Phelan McDermid syndrome, current treatments mostly target epilepsy and anxiety. There has been limited research on this condition.
“During my career, I often meet parents of children with Fragile X and hear how they try to help their children to live a more comfortable life. So, with my experience in behavioural neuroscience, I want to look for safe treatments that might improve behavioural difficulties in children with these conditions.”
Junghyun Choi, Laura Marsal-Garcia, Nahum Sonenberg and Ilse Gantois. FENS Forum / Ilse Gantois
Metformin is the most widely used treatment for type 2 diabetes. In previous research, Dr Gantois and her colleagues have successfully used metformin to treat adult mice that were bred to model Fragile X syndrome. Now the researchers have tested metformin on newborn mice, also bred to model Fragile X syndrome.
This research shows that metformin can correct a biochemical difference in the mouse’s brain that underlies the condition. The researchers also found that metformin stopped the young mice from developing impaired speech, which in mice manifests as very high-pitched squeaking, and repetitive behaviour, which manifests as excessive grooming.
The research team has also used metformin with mice bred to model Phelan-McDermid syndrome and similarly found that they can reduce impaired speech and repetitive behaviour, as well as improving the mice’s impaired learning and memory behaviour.
Dr Gantois and her colleagues gave CBD to mice bred to model Fragile X syndrome from three weeks after birth.
By the time the mice reached adulthood, their repetitive and social behaviours were the same as a control mouse. The researchers found similar improvements when treating mice bred to model Phelan-McDermid syndrome with CBD.
The team are now studying how CBD interacts in the mouse brain to better understand why the drug affects behaviour in this way.
Several other research groups in Canada and the USA are now running patient trials of metformin and CBD for Fragile X syndrome.
Dr Gantois said: “This research and the outcome of the clinical trials could have a major impact on behavioural difficulties that people with Fragile X syndrome and Phelan-McDermid syndrome experience. The major strengths of these studies are that we are using approved drugs that can be taken throughout lifetime and have minimal side effects. Taken at an early age, these drugs could ultimately improve speech delay, social interaction and repetitive behaviour in these developmental conditions.
“Using mouse models makes it possible to look in detail at what is happening in the brain, define the underlying cause of these conditions, and study behaviour and the effect of targeted drugs. Of course, mouse brains are not the same as human brains, however we can often translate the mouse behaviour we study to human behaviours.”
The researchers are also studying the effects of these drugs on mouse models of other autism spectrum disorder-related conditions to see if they could have broader use.
Professor Richard Roche is chair of the FENS Forum communication committee and Deputy Head of the Department of Psychology at Maynooth University, Maynooth, County Kildare, Ireland, and was not involved in the research.
He commented: “We need a lot more research to help us understand conditions like Fragile X and Phelan-McDermid and to find out how these developmental conditions can be treated to give children the best possible chance in life. Mouse models of these conditions give us a vital window into what is happening mechanistically inside the brain and allow us to study the possible benefits of new treatments.”
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