Dr. Maithe Tauber and colleagues at the University of Toulouse Hospital in France have published the findings of a study evaluating the effects of intranasal oxytocin treatment on infants with Prader-Willi syndrome (PWS) in a paper titled The Use of Oxytocin to Improve Feeding and Social Skills in Infants with Prader-Willi Syndrome. (*PWS families - please see note below)
Dr. Tauber has a long-standing interest in determining whether oxytocin might be beneficial for individuals with PWS. Her group was the first to evaluate oxytocin in PWS, showing that a single dose of oxytocin in adults had positive effects on behavior. She has also collaborated with Francois Muscatelli, who is investigating the actions of oxytocin in animal models of PWS. Dr. Muscatelli showed that early administration of oxytocin in a PWS mouse model (Magel2 knockout) dramatically improved suckling and survival in the newborn mice, and has a longterm impact on social skills. Based on those initial findings, and the previous observation of decreased oxytocin neurons in humans with PWS, the French group sought to test whether administering oxytocin to babies with PWS might improve suckling / swallowing (a significant issue for almost all babies with PWS) and social interaction.
In a clinical trial (NCT 02205034) funded by the Hospital University of Toulouse, 18 infants (age 3 weeks to just under 6 months) were given oxytocin via nasal spray. Babies received the oxytocin dose either every other day, once per day or twice per day, for a week. Feeding (sucking / swallowing) and social behavior were assessed one day prior to the start of oxytocin treatment, and then again on the day after the last dose. The study included all genetic subtypes of PWS (deletion, UPD and imprinting mutation).
No safety issues were noted. At the start of the study, all babies had difficulty with feeding (sucking and swallowing) as measured by oral-motor assessment (NOMAS) and videofluoroscopy. After a week of oxytocin treatment, all of the babies, regardless of oxytocin dose, showed improvements in feeding skills, with 88% of them scoring in the "normal" range for the feeding assessments.
The researchers next looked at behavior and social skills. This can be challenging to assess in infants, but they measured aspects such as facial expression, eye contact and interaction with parents. Several measures of social behavior improved after oxytocin treatment (e.g., expression, eye contact, social engagement) while others didn’t change detectably (e.g., vocalizations, attraction). Overall, though, parent-baby interactions were improved after oxytocin intervention.
Finally, all of the infants had brain imaging studies before and after oxytocin treatment, and in the ones that highest quality images for analysis (n=10) the results suggest that there was improved “connectivity” in a specific brain region (superior orbitofrontal cortex, OFC) after oxytocin treatment. The OFC Is important in oral motor skills and in emotional decision making.
When these babies were evaluated later on (at ~2-2.5 years old) and compared to infants with PWS who had not received oxytocin, their overall growth and body composition was similar, as was the age of first walking (~24 months). However, more babies who had been treated with oxytocin were crawling compared to those who had not gotten oxytocin, which may reflect better muscle tone.
The authors conclude that a short course of repeated intranasal oxytocin administration rescues oral feeding and social skills in infants with PWS. Improvement in feeding behavior is particularly important in PWS infants, as aspiration and subsequent respiratory problems are common, and can result in life threatening complications. It’s not yet clear if this short term oxytocin administration will have long term effects, as it seemed to do in PWS mouse models, but this is certainly an area of interest for future studies.
Although the data are very promising, a few limitations should be noted. The study was not "placebo controlled" and it’s possible that the intervention associated with participating in the study may have contributed to improvements in assessments. Also, there was no difference in outcome based on dose. Thus it’s not clear if the lowest dose was “enough” or if the optimal dosing has yet to be reached.
Nonetheless, the good safety profile and positive findings are encouraging and add an important piece to the growing experience of oxytocin in PWS. Looking ahead, confirmatory studies will need to be performed, long term safety will need to be evauated, and additional questions will need to be answered to optimize oxytocin use for PWS. (For example: What is the optimal dose and schedule? Is the benefit applicable to older children, where the results of oxytocin clinical studies have been more variable?) As well, the long term effects of early oxytocin treatment are of considerable interest.
The PWS oxytocin journey continues!
* On behalf of the expert physicians who care for individuals with PWS, please remember that these are early clinical trials. Additional studies are needed to determine if oxytocin is safe in the long term, and if oxytocin shows lasting benefits infants, children and/or adults with PWS. Oxytocin for PWS is experimental and should not be used outside of a carefully monitored clinical study. Additional clinical trials are planned, and participating in a clinical trial is the best way to safely and efficiently determine whether, how and when oxytocin should be used in PWS. Please check out FPWR's PWS Clinical Trials page and join our mailing list to be notified of new clinical studies.