A drug effective on the symptoms of autism in animals raises hope


Caution remains in order. But, if the essay is transformed, it could change the lives of many families. A team of researchers from Inserm, CNRS, Inrae and the University of Tours has just published promising results on a drug that would be effective in improving the interactions of patients with autism. We speak today of autism spectrum disorders (ASD), as this disease which affects neurodevelopment is heterogeneous. These TSA would affect around 700,000 people in France, two thirds of whom are adults. However, there is currently no medicine to help these patients. 20 minutes explains why this publication has something to make you optimistic (but cautious).

What treatment is it?

The research team published an article in April 2022 in the scientific journal Neuropsychopharmacology revealing that bromide ions represent an interesting therapeutic avenue for relieving the symptoms of autism. Knowing that potassium (which belongs to the bromide ions) is already used for epilepsy in veterinarians. “We tested the effect of bromide ions on mice, explains Julie Le Merrer, co-author of the study. In autism, there is a change in the balance between excitation and inhibition in the brain. We tested this molecule, which inhibits the brain, on three models of autistic pathology with different mechanisms. We then carried out the most precise possible behavioral analysis of these mice. And we noticed on the one hand, a restoration of the durations of the contact of the nose. On the other hand, a reduction in the stereotyped behavior of the animals: the mice made fewer circles on themselves. The treatment also reduced the anxiety state of the mice.

In summary, this treatment allowed, on the animal, a significant improvement of three symbolic symptoms of ASD: difficulty of interaction, repetitive movements (stereotypy) and anxiety. And this in the three types of ASD and over the long term.

What are the limitations of the study?

We are talking about preclinical studies for the moment, so only on animals. We will now have to see if human patients react in the same way as mice. “We are coming to the big challenge, admits Julie Le Merrer. So far, autism research has not been very successful, so these early results are no guarantee of success. »

Indeed, one study looked at the effect of balovaptan on the socialization and communication skills of adults with ASD, but the treatment was not effective. Another experimented with oxytocin intranasally, without success. Third failure, this time on bumetanide. “There have been many disappointments over the past two years, summarizes Frédérique Bonnet-Brilhault, head of the psychiatry department at the Tours University Hospital and head of the Autism Center of Excellence. This discourages labs from investing in autism research, when there is a real need. »

Second limit: bromide ions must be used with caution. “There is no addiction effect, on the other hand from certain doses there is a sedative effect, a disorder of vigilance, skin rashes, list Julie Le Merrer. As soon as we see the first signs appear, we stop and they disappear. The problem is that with this drug the margin between effective and toxic dose is small. »

This means that this treatment requires close monitoring, with regular blood tests. “What not all patients with ASD are ready to accept,” she admits. But we looked for a solution which could be to combine the bromide ions with a molecule facilitating the activity of the glutamate receptor mGlu4. This would improve efficiency, give five times fewer doses of each molecule, thus limiting adverse effects and reducing monitoring constraints. »

What are the next steps ?

“We will have to set up a clinical trial on adult patients”, underlines Julie Le Merrer. But the team of researchers is not yet ready and does not yet have a date for the start of this trial.

This clinical trial, if it were conclusive, would make it possible to define the dose to be prescribed and the means of administering it.. For the moment, what is envisaged is an oral treatment, with drops. So easy to take. “In children under 6 years old, it cannot be tablets, but drops”, adds Frédérique Bonnet-Brilhault. In a second step, the researchers could also test the combination of the two molecules.

Why does this result give rise to hope?

“Autism is the only field of medicine where therapy concerns the rehabilitation of language and motor skills, but we are sorely lacking a therapeutic arsenal,” recalls Frédérique Bonnet-Brilhault. The interest with this molecule is that we have a significant effect on the social aspect, an area in which we are very poor, especially since the interventions must start early and are heavy. »

If this therapeutic approach is confirmed, “this pharmacological treatment will not replace the behavioral approaches used today, but complement them, insists Jérôme Becker, researcher at the University of Tours. We are not going to cure the disease but to make life easier for patients, especially adults” for whom early support is rarer. “We will first target children and adults who have a major disability,” explains the head of the child psychiatry department.


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