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Advancing Hope: New Therapies for PWS [2022 Conference Video]

In this video, Dr. Tony Holland, Dr. Lauren Schwartz, and Dr. Deepan Singh discuss two promising studies of new therapies for PWS.

In this 50‑minute video, Dr. Tony Holland, Dr. Lauren Schwartz, and Dr. Deepan Singh discuss two promising studies of therapies for Prader-Willi syndrome: Vagus Nerve Stimulation (VNS) and bright light therapy. The session includes Q&A from participants in the 2022 Family Conference.

Click below to watch the video. If you're short on time, scroll down for timestamps to find the portions you're most interested in.

Presentation Summary With Timestamps

0:59  Advancing Hope New Therapies for PWS

  • Susan Hedtrom’s Introduction of FPWR Board of Directors
  • Introduction of Neil Cowan, Senior VP for Drug Development at Soleno Therapeutics
  • Soleno Therapeutics has been working closely with the FDA and the GCCR and plans to start the randomized withdrawal period for the ongoing Phase 3 study soon.
  • Committed to communicating and updating the community on the progress of the trial.

2:44 Panel: Two Potential Device-Related Therapies: VNS and Light Therapy

  • Two therapies may be able to help our loved ones overcome some significant challenges:behaviors and daytime sleepiness.
  • Panel introduction: Dr. Tony Holland, psychiatrist and professor emeritus at University of Cambridge; Dr. Lauren Schwartz, FPWR research team, and Dr. Dr. Deepan Singh, Adolescent and Adult Psychiatrist at Maimonides Medical Center
  • Working to advance a trial with vagus nerve stimulation.

4:25 Dr. Lauren Schwartz: Vagus Nerve Stimulation (VNS) 

  • We all have a vagus nerve. It starts at the brain and extends through the abdomen and has many branches that go throughout the body, heart and lungs.
  • Sometimes described as a mind-body highway. It regulates a lot of systems and is involved in our emotions.
  • Vagus nerve allows us to have an instant response in situations when we perceive a threat: a near car accident, hearing a noise at night.
  • Your heart pounds and your stomach clenches.
  • Or if you’re being welcomed into a home with friends, it helps relax you. Your heart rate slows.
  • Vagus nerve affects the autonomic nervous system: parasympathetic system and sympathetic system.
    • Parasympathetic  nervous system is the “rest and digest.” It controls when we’re digesting our food and resting and relaxing, and gives us a sense of calm.
    • Sympathetic nervous system is the opposite. It’s involved in “fight or flight” response.
  • The two systems work together to create a kind of homeostasis, or balance, in our ability to respond to day-to-day life.
  • One of the theories about Prader-Willi is that our children may have some difficulties in terms of this system being able to maintain homeostasis. 
  • In particular, people with PWS may go into fight-or-flight mode quickly. They get activated when a threat is perceived and a challenge for our kids is they can perceive a threat or challenge in a lot of situations where others wouldn’t. If school is canceled because it’s snowing or the food plan has changed, or there is worry about changing teachers. 
  • The hope is that this intervention, VNS, will help to regulate this system and could be helpful in giving our children a higher tolerance for coping with life’s ups and downs and unexpected changes.

7:49 History of VNS Treatment

  • VNS has been around for a while. Used most often in seizure disorders. 
  • Two versions: an implantable version that goes into the chest area that was used for many years and a recent external device called a transcutaneous nerve stimulator, which attaches to the arm and connects to the ear via wire and provides stimulation through the auricular branch in that area.
  • VNS treatment has been used for seizures as well as for treatment resistant depression, and there’s established efficacy in both of those areas. 
  • It’s shown to be safe and it doesn’t seem to have negative interactions with other medications that the person might be taking.

8:49 Tony Holland: Why Do We Think This Might Work in PWS?

  • Another function of the vagus nerve is to help control eating behavior. It’s part of the feedback from the gut to the brain that tells the brain that food has entered the stomach and has been absorbed.
  • Our first interest in VNS for people with PWS came about because we thought it might help with hyperphagia.
  • Anecdotal evidence suggests that people with epilepsy who have received VNS treatment have lost weight. 
  • Reasoning followed that there were two theoretical reasons for using VNS for hyperphagia.
  • Did a small study using an implanted device that works like a pacemaker. 
  • Study showed that it did not help the eating behavior, but seemed to help temper outbursts.

10:43 Outcome of Small Pilot Studies on VNS

  • First study was with 3 people, and parents and people with PWS said it didn't have an effect on appetite, but had transformed behavior. Two out of the 3 subjects had problematic behavior.
  • Mother described asking her daughter about delaying lunch, which normally would cause a major outburst. The daughter agreed, and the mother nearly collapsed on the street with astonishment.
  • Daughter eventually got married and said she never could have coped with the stresses of wedding planning without the treatment.
  • Problem was that the first study was designed to look at eating behavior so researchers didn’t collect much information on temper outbursts and other behaviors.

13:02 Results of Second VNS Study

  • Tony Holland: In a second study using the external stimulator (worn 4 hours a day), 4 out of 5 people who completed the study reported benefits in behavior.
  • This study was aimed at behavior and not overeating, so the hope is that a new study planned through FPWR will improve temper outbursts.

13:56 Hope for Continuing Research

  • Dr. Holland: One of the very striking things was that the participants in the two studies — the implanted device and the external one — was that parents said to us, “You know, it may not have helped the eating directly, but we can now reason with our son or daughter and say to them, ‘Look, we really do need to control your access to food,’ or ‘You need to be on a diet.” And they would accept it in a way that they would not have done before; they would have argued and fought over that particular issue.
  • So there’s an expectation that we’ll see improvements beyond the outbursts, but how far that extends remains to be seen. 

14:53 Will VNS Affect the Need for Medication?

  • Q: So many of our loved ones are on a cocktail of medications in an effort to control or manage some of these more challenging behaviors. What do you think we might see from the use of VNS as it relates to the need to have those medications?
  • Dr. Holland: If those medications have been started because of the behavior, I think that it’s likely that if people benefit from VNS those medications can be reduced and perhaps stopped. That would need to be done carefully.
  • If someone improves on VNS, what I would say is I would reduce any medication that had been given for the outbursts to see whether things remained okay or not.

25:49 Why Are We Excited about VNS?

  • Lauren Schwartz: Ever since I heard the first study from Dr. Holland, I was ready to fly to the UK to get one for my daughter. 
  • I’m really excited about it, but things take a long time in research.
  • Research on temper outbursts, or emotional outbursts, shows that they’re common in people with PWS, especially as they get older. 
  • Teens and young adults struggle with these behavioral challenges and they really affect quality of life for the person with PWS and their family.
  • Temper outbursts can affect school work, being able to hold down a job, and living situations such as supported living.
  • Getting along with others and accepting guidelines can present a problem, and we don’t have a lot of good treatments right now for these emotional outbursts. 
  • Having a treatment, especially one that is relatively safe and doesn’t seem to have many side effects, if any at all, could be a real game-changer for people with PWS and their families.
  • As families, many of you struggle at home with some of these challenges and it affects everybody: the siblings and the parents. So the treatment could have an added benefit of improving the quality of life for the hole family.

17:44 Plans for a FPWR Clinical Trial

  • In order to make VNS treatment available in the US, there needs to be a larger study to prove efficacy.
  • Trial will be done in multiple sites, ages 10 and above, at the age where emotional challenges intensify.
  • 40 years old will be the cutoff.
  • Study will be recruiting sometime next year, and will need a lot of subjects, so hopefully, people will volunteer to be screened.
  • Another requirement to be in the study is that parents will be expected to monitor temper outbursts and monitor other behaviors throughout the study.
  • Study will likely last a year.

18:59 Will the Trial Be In-Person or Remote?

  • In order to increase access for families, the hope is to make the study as remote as possible.
  • It will likely require one in-person visit at the beginning for assessment and training on the device.
  • The rest will probably be remote, with a possible in-person visit at the very end to finish out the study.

20:17 What Can Families Do?

  • Families can help fundraise for the study because FPWR will be funding the study.
  • Families can participate and just spread the word to people in the community who might be interested.

20:42 Buyer Beware

  • There are devices out there that claim to be vagus nerve stimulators. 
  • Be careful, because the vagus nerve runs from a particular part of the ear, and if the electrode doesn’t stimulate that bit, it’s probably not stimulating the vagus nerve.
  • Experts advise against going out there and buying one yourself.
  • Study will be using a particular one that is manufactured in Germany.
  • Want to make sure we are using the proper tools.

21:34 Bright Light Therapy for Excessive Daytime Sleepiness

  • Dr. Deepan Singh, Adolescent and Adult Psychiatrist at Maimonides Medical Center
  • If you have a child who’s going to school or who’s taken a long trip with you, or even a short trip to the store, you know that excessive daytime sleepiness is very common.
  • More than half of all patients with PWS have excessive daytime sleepiness. 
  • Despite having a good 7 + or even 9 hours of sleep at night, your loved one with PWS will be falling asleep sometimes.
  • It can be drastic enough that you’re having a conversation with them and they’re nodding, or they’re nodding off while watching TV or at a meeting like this. 
  • Sometimes folks are falling asleep on the floor, and it’s disruptive and can sometimes lead to other behavioral issues such as trying to fight sleep and getting irritated and angry and lashing out.
  • There seems to be a genetic cause for excessive sleepiness.

23:25 Reasons for Excessive Daytime Sleepiness in PWS

  • Could be related to
    •  sleep apnea
    • weight gain 
    • Low muscle tone
    • Obstructive Sleep Apnea (OSA) where the airways are not open enough for the brain to be awake
    • Central sleep apnea, which is a problem with oxygenation
  • The above could be caused by the genetics of PWS

24:35 The Use of Chronotherapy 

  • Scientists in Tennessee and at UC Davis are testing the use of chronotherapy, which is resetting the biological clock and seeing how it might affect metabolism and activity
  • FPWR funded Dr. Singh’s research on using bright light therapy to look how it might impact daytime sleepiness.
  • Bright light therapy is one of the well-established ways of treating sleepiness in patients with Parkinson’s Disease, traumatic brain injury, or Alzheimer’s Disease. They have sleepiness as well, and very often light therapy is used effectively in these populations. 
  • The lack of studies of light therapy in PWS made Dr. Singh wondered if it should be tested in people with PWS.
  • Study is based in basic science research and clinical research conducted in other settings.
  • Light devices are available right now. We don’t need to have them manufactured or go through the FDA to get 10,000 things done. These are over-the-counter devices that have the full spectrum of bright light.
  • Full-spectrum bright light is almost like sunlight, and it stimulates the same kind of changes in the brain that exposure to sunlight would cause and seems to help keep people awake.

27:02 Details of the Study

  • Studying bright light therapy in children 6-18 years old.
  • Reason for the age is that parents are more likely to have them sit in one place for two time periods during the day: in the morning and in the afternoon.
  • You shouldn’t stare right at the lamp, but the lamp can be put in the general gaze direction of the child as they’re engaging in some activity like solving a puzzle.
  • Duration is about 8 weeks.
  • Hope is that people can keep the device after the study period, but if there’s a lot of interest and we have to reuse devices, we’ll make sure that we cover shipping costs.
  • Because travel disrupts circadian rhythms, the study will be done remotely. 
  • Devices will ship to people after a two-week period to determine if the child meets criteria for excessive daytime sleepiness.
  • That will be determined by a sleep diary.
  • Doctors will also help determine if the participants have any eye difficulties that would make it difficult.
  • The other exclusion criteria would be if you’ve tried bright light therapy in earnest before and it hasn’t helped your child.

31:27 Q&A

FPWR Enewsletter

Topics: Research

Susan Hedstrom


Susan Hedstrom is the Executive Director for the Foundation for Prader-Willi Research. Passionate about finding treatments for PWS, Susan joined FPWR in 2009 shortly after her son, Jayden, was diagnosed with Prader-Willi Syndrome. Rather than accepting PWS as it has been defined, Susan has chosen to work with a team of pro-active and tireless individuals to accelerate PWS research in order to change the future of PWS. Inspired by her first FPWR conference and the team of researchers that were working to find answers for the syndrome, she joined the FPWR team in 2010 and led the development of the One SMALL Step walk program. Under Susan’s leadership, over $15 million has been raised for PWS related research.