Two newly published studies are suggesting modulating activity of the hormone vasopressin may help treat the social impairments associated with autism. The two clinical trials use different approaches to target vasopressin, and while both are reporting positive results, some experts are suggesting it is too early to conclude these hormone treatments would be beneficial to all autistic subjects.

Vasopressin is a hormone produced in the brain by the hypothalamus. It serves a number of different functions including playing a role in regulating blood pressure and body temperature. Vasopressin is structurally similar to another hormone called oxytocin, and both compounds have been found to be strongly related to human social behaviors.

In the first study, a team from Stanford University School of Medicine trialled the effects of a nasal vasopressin spray on a small group of children with autism. The 17 children, aged between six and 12, were given daily treatments of vasopressin for four weeks. Behavior was evaluated at the beginning and end of the treatment using a questionnaire called the Social Responsiveness Scale (SRS-2).

Compared to a control group of 13 children receiving a placebo, the vasopressin group displayed significant improvements in SRS-2 measured social abilities. Perhaps most interesting was the observation that the biggest improvements in social abilities came from children with the highest vasopressin levels at the start of the study. This almost contradictory response suggests either the children with lower starting vasopressin levels needed a higher dose or there are other factors that determine the efficacy of the treatment.

The second study reports the results of a Phase 2 clinical trial for a drug called balovaptan. The drug has been designed to block a certain receptor in the brain that responds to vasopressin. The hypothesis is that excessive vasopressin activity may be responsible for some overactive autistic behaviors, and animal studies have found that blocking vasopressin brain receptors can reduce heightened emotional responses.

The balovaptan trial encompassed over 200 adult men with autism spectrum disorder, split into four groups: three different dosage arms and a placebo control. These results were somewhat mixed, with no improvements identified using the SRS-2 scale after 12 weeks of treatment. The study does note however that meaningful improvements were found using a secondary measurement called the Vineland-II Adaptive Behavior Scale.

The balovaptan trial was run by Roche Pharmaceuticals, the drug developer behind the new compound. Further balovaptan trials are currently underway to try to generate more data as Roche moves the drug toward an approval stage after receiving a Breakthrough Designation for the treatment from the FDA back in 2018.

One problem these two trials certainly raise is the challenge of establishing clear efficacy measures for drugs designed to treat autism. James Cusack, from a UK autism research charity called Autistica, suggests that while it is clear vasopressin-based treatments may be helpful for some, it is unclear exactly who it will best benefit and to what outcome.

"It's important to remember that in the larger [balovaptan] trial the researchers didn't find this drug was effective on the main measure they chose, so another trial is needed to establish how valid this finding is," says Cusack. "We need more research to understand whether this treatment makes a difference to daily living skills and who benefits most."

Antonio Hardan, senior author on the Stanford study, agrees that more work needs to be done to better understand exactly which patients will benefit and what specific behavioral improvements the vasopressin treatments are aiming for.

"Is it motivation, affiliation, attachment? Ability to understand others' mental states or read facial expressions or body language? Identifying who responds and why is really important," says Harden.

While both studies are reporting no major adverse effects it is clear the disparate results point to the need for more research. Both blocking and boosting vasopressin does seems to confer social improvements in some autistic subjects, but until larger trials are completed it is unclear exactly what kind of treatment best suits certain people.

The Stanford study was published here in the journal Science Translational Medicine.

The Balovaptan study was published here in the journal Science Translational Medicine.