Can handling a "social" hormone activity treat autism? | Science

Many people with autism find it hard to look in their eyes, read the emotions of other faces and share their affection. And no drug is approved to treat such social deficiencies. Now, the results of a small university clinical trial suggest that increasing levels of vasopressin – a brain-active hormone known to promote binding in many animals – can improve the social deficits of children with autism. But in a confusing twist, a larger company-sponsored trial that took the opposite approach, tying down the effects of vasopressin, also revealed some improvements in autistic adults.

"I have never seen this before," says Kevin Pelphrey, a neuroscientist studying autism at the University of Virginia in Charlottesville, about the conflicting results. He and others say that the vasopressin blocking approach does not have much support from previous animal research. The new study showed some advantages but failed to reach the main criterion defined by the researchers. Nevertheless, he says, both studies suggest that vasopressin signaling in the brain plays a key role in autism and "gives me a lot of renewed excitement" for the treatment of the disease.

Although vasopressin appears to stimulate social bonds in animals, the activity of the hormone in the brain is not fully understood and its effects vary according to species and context. Blocking its activity in the brain of some rodents prevents them from forming an attraction for a partner. But in a species of asocial hamster, the injection into the brain of a man seems to stimulate aggression.

Another brain signaling molecule of very similar structure, oxytocin, is already under study for the treatment of autism. But vasopressin has attracted less attention. Recently, Karen Parker, a neuroscientist at Stanford University in Palo Alto, Calif., And her colleagues found evidence that less social apes – who tended to stay away from peers, for example – also had high rates. vasopressin lower in their body. cerebrospinal fluid. The group also found that autistic children with the highest social disability also had the lowest rates of vasopressin.

The Stanford team therefore administered a nasal spray containing vasopressin to 17 autistic children aged 6 to 12 years. Thirteen other children with autism served as a control group and received a placebo. Before and after the 4-week treatment, the research team asked parents to rate the children on a questionnaire called the Social Responsiveness Scale (SRS-2), which asks how often children "would prefer to be alone with others", for example and how often they "avoid eye contact". This 65-item scale gives sex-adjusted scores of 37 to 90 for girls and 38 to 90 for boys.

Children treated with vasopressin showed significantly greater improvement – a seven-point reduction in SRS-2 than those in the placebo group, the team reported today. Translational medicine science (STM).

These results "are very interesting", especially because the team has not noticed any major side effects, says Angela Sirigu, neuroscientist at CNRS, the French research agency in Bron. , who also studies neurohormones for the treatment of autism.

Children with higher vasopressin blood levels at the start of the Stanford study experienced greater improvements. Sirigu says it's counter-intuitive: you expect children who miss the most hormone to benefit the most from this stimulation. According to Parker, these children may have needed a higher dose or longer treatment to reap the maximum benefit. Or maybe the blood vasopressin is a marker of another feature still unknown to children, which predicts the improvement of their treatment.

The only weakness that Pelphrey found in Stanford's study was the size of his sample: "If it were double, I would jump up and down." Still, he adds, "I'm pretty excited in my chair. "

The second trial, meanwhile, tested a very different hypothesis on vasopressin. Although many people with autism have difficulty interpreting and exchanging emotions, they also sometimes have hyperactive emotional reactions, says neurologist Paulo Fontoura of Roche Pharmaceuticals in Basel, Switzerland. And vasopressin could drive these answers, he suggests. In a rat autism model, blockade of a vasopressin receptor appeared to reduce the abnormally high brain response of the animal to the presence of a juvenile rat. In the new trial, the Roche team recruited 223 autistic men to test a compound called Balovaptan that blocks a receptor for vasopressin in the brain. The 148 men who took the drug improved on an SRS-2 assessment, but those who received a placebo improved in the same way, announced today the team. STM. Fontoura and colleagues say that the strong placebo effect of the study suggests that SRS-2 is not the best way to measure social improvements. Men receiving Balovaptan showed significant improvements over the placebo group on a different test of autism symptoms, called Vineland-II.

The authors of both studies suggest that there could be significant differences among their participants. Maybe some people with autism might benefit from stimulation of vasopressin and others from blocking it.

The Stanford group is currently conducting another trial of vasopressin to enroll 100 children. Roche has two ongoing Balovaptan trials – an initial test in children and a larger study in adults to demonstrate the effectiveness of the drug to regulators. "It's too early to make a head-to-head comparison," says Fontoura. "Only when we have more data will we be able to draw conclusions about the best way to proceed."