Oxytocin as a promising potential treatment in PWS: An opportunity to help advance the next step

 Oxytocin is a hormone that has a number of important functions.  It gets thing rolling in childbirth – sending moms into labor, but also helping set the stage for the bonding that will occur in the newborn period.  It’s been referred to as the hormone of love – it increases trust, optimism and social interaction.  Because of this, it is being studied as a potential treatment for autism, schizophrenia and social anxiety in Fragile X syndrome, among other things [Green and Hollander, 2010].  Intriguingly for PWS, oxytocin also plays a role in appetite control, with increased levels of oxytocin associated with decreased appetite [Leng, 2008].

In PWS, it has been reported that the number of oxytocin-producing neurons in the hypothalamus is reduced [Swaab, 1995].  Given the important role of this molecule in modulating social behavior, it’s possible that abnormally low oxytocin might underlie some of the poor social adjustment, behavioral problems and autistic tendencies in PWS.  If that’s the case, administering oxytocin might be a new therapeutic option for PWS.  Prof. M. Tauber and colleagues at the Reference Center for PWS at Children’s Hospital in Toulouse, France have begun exploring this hypothesis, investigating the potential of nasal oxytocin to improve behavior in PWS [full article available here: Oxytocin may be useful to increase trust in others and decrease disruptive behaviours in Prader-Willi syndrome: a randomized placebo-controlled clinical trial in 24 patients].  This first clinical trial of oxytocin in PWS focused mainly on establishing that oxytocin is safe to administer to individuals with PWS, and thus a single dose was given and the effects monitored.  Although the study was relatively small, the trial design was stringent – a so called “double blind, randomized, placebo controlled crossover” study – meaning that neither the patient/caregivers or medical staff knew which spray was the oxytocin and which was the placebo control, and every patient got either oxytocin then placebo, or placebo then oxytocin.  Such a design protects against bias and includes data points for each patient on both the treatment and placebo.  This is particularly important in a clinical trial that will measure outcomes such as improvements in behavior, which can be tricky to measure and are somewhat subjective. 

For the study, 24 adults with PWS received oxytocin or placebo nasal spray and were then given social skills test, and also monitored for general behavior (trust, sadness, interpersonal conflicts) over the next two days.  Overall, the oxytocin was well tolerated and didn’t cause any medical problems.  There was a tendency toward improved social skills test scores in individuals after oxytocin treatment, but the difference compared to the placebo wasn’t significant.  However, significant improvements in behavior were noted in the two days following oxytocin administration, as measured by increased trust, decreased sadness and less disruptive behavior.  Although only anecdotally documented, there did seem to be decreased appetite in some individuals after treatment.  This is an exciting preliminary finding for those with PWS, suggesting that oxytocin might have promise for improving some of the most challenging aspects of PWS.  

So, what are the next steps??  Clearly the study needs to be repeated with a larger group of PWS individuals, and with longer-term administration of oxytocin.  As well, issues such as dose and timing of doses are critical to determining whether the positive effects can be optimized.  Finally, it would be nice to gain an understanding of what oxytocin is doing in the brain as a means of more rationally developing it as a therapeutic for PWS.  We are fortunate that Dr. Tauber and her group have already considered these questions and more, and have designed a follow up clinical trial of oxytocin administration in young adults with PWS.  They plan to use brain imaging analysis to better understand the effects of oxytocin administration and will more fully explore the effects of oxytocin on behavior and appetite.  FPWR is very excited to have the opportunity to fund this important clinical study, and we invite your help!  We’ve developed a fundraising “puzzle”, with all of the funds going directly to support this study.  Please consider purchasing a puzzle piece in honor of someone you love with PWS.  Each piece can be purchased for $500 – if you’re fortunate enough to have the funds to buy a piece (or two) outright, please consider it.  If not, perhaps it can go on your Christmas list or you can gather a group and purchase one together. 

Many thanks for all of your generosity as we work together to eliminate the challenges of PWS!