[ad_1]
Two drugs that alter the activity of vasopressin hormone appear to improve social communication in people with autism. The results come from two independent clinical trials published today in Translational medicine science.
The results are encouraging, but some experts recommend caution, saying that the methods used to evaluate drugs were not designed for this purpose.
Vasopressin is linked to oxytocin, a hormone believed to regulate social bonds. But the link of vasopressin with autism is far from simple: there is evidence implicating too much and too little hormone in people with the disease.
Both drugs also target vasopressin in the opposite way. One of them, balovaptan, blocks a receptor for vasopressin in the brain and slows down the activity of the hormone. The other is a nasal spray containing vasopressin. Despite their opposing modes of action, both drugs appear to enhance social function in autistic people; nor has any serious side effects.
The results are remarkable because no drug is available to treat the fundamentals of autism, says Eric Hollander, professor of psychiatry and behavioral science at the Albert Einstein College of Medicine in New York, who was not involved in any of these studies.
"These two studies provide important insights into the importance of vasopressin or vasopressin and oxytocin systems in social communication," he says. "Different agents affecting these systems might ultimately be useful in terms of new treatments for autism."
Nevertheless, both studies are based on a questionnaire that is not designed to measure the effectiveness of a drug, says Lawrence Scahill, director of clinical trials at the Marcus Autism Center in Atlanta.
"These two studies suggest that the mechanism deserves further study," says Scahill. "But I think we want to be careful not to overinterpret the results."
Dose effect:
In the Balovaptan trial, led by the Swiss pharmaceutical group Roche, researchers from 26 sites across the United States randomly assigned 223 autistic men to the drug once a day for 12 weeks. The pills contained 1.5, 4 or 10 milligrams of balovaptan or a placebo.
Men who took balovaptan did not perform better than controls in a caregiver questionnaire called the Social Responsiveness Scale, the primary endpoint of the study. But people taking the two highest doses improved their social and communication skills, based on Vineland's adaptive behavior scales, a secondary measure. Men showed no difference on scales measuring repetitive behaviors, anxiety or mood, among other traits.
Roche researchers were not available to comment, but Hollander says these results are promising.
"It's hard to show good response rates in multisite trials, where placebo responses and site effects are high," says Hollander. "But they have a nice dose-related effect on this area of social communication."
The test results prompted the US Food and Drug Administration to grant the drug "revolutionary" status to the drug in January 2018. Researchers are testing the drug in two new clinical trials: one on autistic children in the United States, the other on adults Europe, Canada and the United States
Sniff test:
When testing the vasopressin spray, parents of autistic children aged 6 to 12 administered a nasal spray to their children twice a day for four weeks. Of the 30 children participating in the trial, 17 received the vasopressin spray and the others sniffed a placebo.
The children of the vasopressin group have significantly improved their social skills, based on the scale of social responsiveness, the main measure of outcome. Assessments of these abilities by clinicians, parental anxiety assessments, and children's performance on two of the four social cognition tests also showed improvement. None of the children who have had vasopressin has become more aggressive, as some rodents do.
"Many independent evaluations show that the drug was more effective than placebo," said Karen Parker, senior associate researcher, associate professor of psychiatry and behavioral science at Stanford University in California.
Paradoxically, children with the highest vasopressin blood levels prior to treatment tended to show the most significant effects, and only these children improved their repetitive behaviors. Parker does not know why, but the dose may have been too low to benefit people with less vasopressin, she says.
Clinical warnings:
Some experts, including the researchers themselves, warn that the results are preliminary and need to be repeated in larger groups of children.
"The results of a small study can be misleading," says Scahill. "And when you have so many outcome measures in a small study, it's possible that some things become statistically significant by chance."
Others wonder how two drugs with opposing modes of action can have similar effects.
"These are very different approaches to targeting the vasopressin system," says Elizabeth Hammock, assistant professor of psychology and neuroscience at Florida State University in Tallahassee. "And we do not know for sure how it works."
Experts note, however, that it is difficult to compare tests with such different conceptions and sets of participants.
"Autism is a very heterogeneous disorder," says Antonio Hardan, a professor of psychiatry and behavioral science at Stanford University, who led the nasal sprays trial. "It may be possible, with autism, to see abnormalities related to either too much vasopressin or too little."
Hardan and Parker test the spray in a new test of 100 autistic children.
MORE READING
This story was originally published on Spectrum.
[ad_2]
Source link