Can bromide ions, an ancient anti-epileptic drug, relieve people with autism spectrum disorder (ASD), by reducing symptoms that severely impact social behavior?
That’s the pathway that researchers from Inserm, CNRS, Inrae, and the University of Tours, discovered in a study published in April in the journal Neuropsychopharmacology. This is promising as therapeutic research in autism struggles, as several clinical trials (those for lovaptan, intranasal oxytocin, and bumetanide) were recently abandoned.
“Autism spectrum disorders are a change in the balance between neuronal excitation and inhibition (in favor of increased excitability). This imbalance is also observed in epilepsy, which is also a frequent co-morbidity of autism. Because bromide ions have long been used as antiepileptics (because they facilitate the inhibition of neurons) We wondered if it could rebalance ASD and relieve symptoms.”explained during a press conference on June 16, researcher and co-author, Julie Le Merrier (iBrain, University of Tours, CNRS).
Three models of the mouse
One of the origins of this work is the consideration of three mouse models, autism has heterogeneous origins: the first does not express mu-opioid receptors, the second has fragile X syndrome, and the third, Phelan-McDermid.
Another peculiarity: the researchers conducted a behavioral analysis of mice (not just cells), since “Autism is diagnosed in humans primarily through behaviour.” Julie Le Maire confirms. In particular, they looked at the mice’s social interaction (do they touch their piles when they don’t know each other?) and stereotypical behaviors (how many circles they make).
consequences : Bromide ions act on these two diagnostic axes for autism: they improve social behavior and reduce stereotypes in the three different genetic models., We read. It also reduces anxiety due to its already known calming effect.
Towards dual therapy?
“The big challenge now is to move from mouse to human”summarizes Julie Le Maire–a milestone that recent clinical trials have failed to meet. “We are optimistic because we have considered several mouse models. This allows us to be more confident about the treatment’s ability to be generalizable to multiple subsets of individuals with autism. But we remain cautious.” Adds Jerome Baker, co-author and researcher Inserm.
Although no release date has been set, the process of building a clinical trial is underway. Apart from the regulatory aspect, it is a matter of group composition (a small number of adult patients, with severe symptoms), the determination of the criteria, the determination of the doses and frequency of administration (for every operating system), to mobilize the actors … in particular the pharmaceutical companies.
In the long term, the researchers hope to be able to combine bromide ions with other molecules, particularly one that facilitates glutamate receptor (mGLU4) activity and slows excitation. The synergistic effect could allow to reduce the doses of the two drugs and the adverse effects, especially for the doses of bromide ions, which have a narrow therapeutic window. “The margin between the effective dose and the toxic dose is small, and this requires careful monitoring of patients, with regular doses of bromine by blood test. Which can be restrictive, especially for adults with autism spectrum disorder »Julie Le Maire explains.
The combination has already been tested in mice, as well as in cell models, with positive results that are maintained over time, while the doses of each compound have been divided by five. “Testing this combination in a human clinical trial would take longer”However, the researcher specifies.
In any case, these therapies are not intended to replace the targeted interventions, upon which the management of ASD today depends. “They will never target people for whom autism is a feature. It primarily targets children and adults with significant disabilities.comments by Pr Frédérique Bonnet-Brilhault (Children Psychiatrist, Head of Exac-T Center of Excellence for Autism at CHRU Tours). “It’s not about curing a disease, it’s about relieving symptoms and making life easier”Julie Le Maire adds.
Autism affects 1% of the general population, or 700,000 people in France. Research on ASD goes far beyond the pharmacological pathway: developing very early diagnoses (from six months), contributing to new technologies, or studies on the risk of developing a neurodegenerative disorder during old age.
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