Science Concentrates NEUROSCIENCE
Autism trials show promise
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2 studies focus on the hormone vasopressin and its receptor in the brain
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O NH of the hormone getting into the brain. H2N Many people with autism struggle to unO NH S derstand social cues and facial expressions, The trial was randomized and douHN O S ble-blinded, so neither parents nor leading to difficulty with social interacO doctors nor researchers knew which tions, which impacts their quality of life. NH2 NH N O H child was getting the drug and Current treatments for autism focus N H which was getting the placebo on improving mood because trouble with N O NH2 O H2N N (Sci. Transl. Med. 2019, DOI: social interactions can lead to irritability O H O O 10.1126/scitranslmed.aau7356). and depression, says neuroscientist Karen After the 4-week trial, the children took Parker of Stanford University. Currently, Arginine vasopressin several tests, including one that asked there aren’t many pharmacological soluthey wanted to avoid side effects by makthem to interpret emotion from facial feations to address autism’s core feature, ing sure that it didn’t interact with the tures. Their parents and doctors reported the social deficits, she says. That may be vasopressin receptor in the kidneys. whether the kids showed any improvechanging. The results of two recent clinIn the Phase II trial, 223 men were given ment in communication or social cues. In ical trials suggest that a hormone called either a placebo or a dose of balovaptan all tests, Parker says, the children who got arginine vasopressin (or simply vasopresfor 12 weeks. The results were not as clear vasopressin did somewhat better than the sin) and a small molecule that targets as the vasopressin trial in children. For children who got the placebo. one of its brain receptors might mitigate example, the researchers saw no change In the parent report, some social deficits in N O in SRS-2 test scores in the adults. But in a called the Social Responpeople with autism. The different test, the Vineland-II test, which siveness Scale-2 (SRS2), results, says Karen Bales, a N measures communication and daily living children treated with behavioral neuroscientist N skills, they saw a change. vasopressin improved at the University of CaliN “We got a five-point increase in three by seven points more fornia, Davis, who was not months,” Fontoura says, pointing out that than children who got involved in the studies, N Cl this test is often used as a measure of imthe placebo. Parker says mimic what she and othCH provement in people with autism underan improvement of 10 or ers have seen when study3 Balovaptan going behavioral therapy, and that it can more points is considered ing vasopressin-related take up to two years to get a three-point clinically significant. In the facial features behavioral changes in lab animals. test, the children given vasopressin scored improvement. “We have so few approved treatments The US Food and Drug Administration five points higher than children on the plafor autism, and the ones we have are has given balovaptan a breakthrough cebo. Children receiving the placebo had really just for sort of secondary things, designation, and Fontoura says the Roche an average score of –1, while children on like irritability, that come along with not team is now recruiting children for their vasopressin had an average score of 4. The being able to communicate effectively,” next trial. highest possible score is 28, Parker says. Bales says. “So it’s very exciting to see a One thing that remains to be explained The evidence from the three tests and repotential treatment for one of the core is how a treatment that activates the vaports suggests that vasopressin improved symptoms.” sopressin receptor and one that inhibits the children’s social behavior, Parker says. Vasopressin is a nine-amino-acid horit can have similar effects in people. UC Parker’s team is continuing with a largmone that is made in the brain and has Davis’s Bales points out that vasopressin er trial, and to overcome any possible submany functions in the human body. It acts can bind the oxytocin receptor, which is jectivity in results, they are adding brain on the kidneys and reduces urination, but also involved in social interaction. This activity and eye-tracking measurements. in parallel with another hormone, oxytononspecific binding by vasopressin may In the other trial, Roche Innovation cin, it regulates emotion in the brain. In explain some of the results in the child previous studies of healthy people, a spritz Center researchers tested a small molstudy. ecule called balovaptan in adult men of vasopressin up the nose seemed to enResearchers will also need to deterhance memory, especially of faces express- with autism. Balovaptan acts opposite to mine when to deliver such treatments, vasopressin—it inhibits the arginine vaing some sort of emotion. After discoverBales says. Fontoura agrees, adding that ing that people with autism tended to have sopressin receptor 1A (V1A) in the brain people might not take such drugs daily, (Sci Transl. Med. 2019, DOI: 10.1126/scilow levels of vasopressin in their cerebroinstead taking them at specific times in translmed.aat7838). spinal fluid, Parker and her team decided anticipation of a social event. A child at “Being able to really find a molecule to test it on children with the disease. home may not need it, while a child in that was specific to V1A was really a feat In their pilot study, the researchers school or a young adult going for a job inof chemistry,” says Paulo Fontoura, the treated 30 children, mostly boys ages 6 Roche scientist who led the trial. Fontoura terview might want to take something, he to 12, for 4 weeks with nasal spritzes of says.—MEGHA SATYANARAYANA says that when developing the molecule, vasopressin, which improve the chances
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C&EN | CEN.ACS.ORG | MAY 13, 2019
