FPWR 2010 Conference Wrap-Up

The annual FPWR conference was held in Bethesda, MD on Sept 11-13, 2010.  There was time to celebrate the successes of the past year, socialize with friends old and new, share ideas about raising funds and raising our children, and plenty of time to learn, from the scientists themselves, about exciting PWS research that will impact our children.  A summary of the events is provided below.

Saturday Evening

Jessica Howard, FPWR Board member, kicked off the conference with a celebration of successes for the PWS community this year.  

We have so many accomplishments to celebrate! The Research Strategy Workshop held in November 2009 was a huge step forward for the PWS research community.  The event gathered 65 top scientists from around the world who specialize in PWS and related fields. They created a comprehensive research strategy, or “blueprint” for PWS research. The event was sponsored by FPWR, the National Institutes of Health, the Canadian Institutes of Health Research, PWSA USA, and FPWR Canada.

A national PWS Awareness month was established by House Resolution 55 and Senate Resolution 543. Many people helped make this happen, including FPWR supporters who “Hiked the Hill” in Washington, DC at past FPWR conferences. Special thank yous go to Amy Porter and Peter Fleischmann!

FPWR supporters held fundraisers, big and small, and ALL were crucial in helping FPWR fund research.  Events & supporters over the past year included:

  • California State Society Golf & Tennis Tournament: $167,000 in Sept 2010
    • Another big thank you to the amazing Amy Porter!
  • Marine Corps Marathon 2009: Five runners raised $13,000! 
    • Runners were: Adrian Connerty, Amy Porter, Todd Porter, Rick Spees.
    • Tom Howard ran the Marine Corp 10k & raised $7,000
  • Go the Extra Mile Walk: Shawn & Rachel Johnson raised $14,000!
  • One SMALL Step Walks: There were several walks across Canada, the US and UK in August 2010. Keegan and Tanya Johnson shared those exciting details in a separate presentation, but overall, this amazing event raised more than $200,000!  
  • Macy’s Shop for a Cause: multiple locations & supporters raised $2,000!
  • Beef & Beer and a Golf Tournament: Mike Stermel raised over $5,000!
  • Letter Writing Campaigns:
    • Tom & Renay Compere raised $2,000
    • Mark & Robin Greenberg raised $10,000 in support of the PWS Research Strategy Workshop
    • Sergio and Alice Viroslav, along with their daughter Olivia, who asked for donations for her Bat Mitzvah instead of gifts, raised $13,000 (and another $10,000 went to a children’s hospital in Israel!)
  • Kentucky Derby: PWSA Colorado donated $50,000 of the funds raised to FPWR!
  • Myrtle Beach Marathon: Janet Gulley raised $1,800
  • May PWS Awareness Month virtual fundraising event:
    • Sharon Montecalvo raised $465
    • April & Travis Steffan raised $265
    • Kara Unfried raised $655                                                    
  • All of these events, plus direct donations from many supporters, enabled FPWR to fund seven projects, totaling $300,000 for 2010!! This brings FPWR’s total since 2003 to 40 projects and $1,600,000!!

Dr. Connie Lee was our keynote speaker for the evening.  Connie told of her experience being plunged into the world of special needs parent when her young daughter was diagnosed with cerebral cavernous angiomas (CCA). Upon receiving the diagnosis, Connie realized that there were very limited resources for individuals and families facing this rare disorder of blood vessels in the brain and spine.  To address that deficiency, Connie founded the Angioma Alliance, a nonprofit patient organization for individuals and families dealing with this disorder. The Angioma Alliance provides a range of services, from patient and family support to working closely with the scientific community to advance research into the causes and treatment of CCA.  Connie shared their organization’s experiences in developing systems that worked for their needs and for the needs of the research community, and offered tips on using limited funds to maximize scientific advances.  The Angioma Alliance sponsors an annual scientific workshop and they have worked with the researchers to build a highly collaborative environment in their field.  A significant obstacle identified by researchers was limited access to vital patient tissue samples, which are needed to elucidate the underlying cause of angioma development.  In response, the Angioma Alliance developed an advocacy–owned DNA/Tissue bank and a patient registry.  Through the tissue bank, they collect tissue, maintain clinical information, perform DNA diagnostics, protect patient privacy, and distribute tissue to the research community.  Connie’s captivating talk was a wonderful opportunity to learn about how best to address some of the challenges FPWR faces as it seeks to advance the science of PWS.

Sunday

Dr. Ron Cohn is an Associate Professor of Pediatrics, Neurology and Genetic Medicine at Johns Hopkins Medical Center, and is Director of the Johns Hopkins Hypotonia Center , the only clinical and research center in the world that focuses specifically on understanding and treating hypotonia.  He sees children with any one of the more than 500 genetic conditions that lead to hypotonia, and thus he has a unique perspective on how “PWS hypotonia” is the same or different from hypotonia in other disorders.  He did a wonderful job of explaining the intricacies of hypotonia, including the difference between tone and strength.  His perception is that hypotonia in PWS has both a central component (ie, an abnormality in tone, disruption of how the message goes from the brain to the muscle) as well as a peripheral component (ie, reduced muscle strength/abnormal muscle composition).  He spoke about what might underlie the abnormalities in PWS muscle and tied that into his research looking at master regulators of muscle development, maintenance and regeneration.  He also showed some great video of hibernating ground squirrels, his favorite research subject, which have the interesting biological problem of needing to maintain muscle strength and integrity despite extensive periods of inactivity.   Reflecting what was discussed at the PWS Research Strategy Workshop last fall, he acknowledged the lack of research focused on the origin and long-term consequences of hypotonia in PWS, and felt this was an area ripe for investigation.  With respect to practical advice for hypotonia in PWS, he strongly supported physical therapy including aquatherapy and hippotherapy, and discussed the careful use of supplements.  He indicated that strategies to increase muscle mass, currently an active area of investigation and pharmaceutical development, might have eventual application to hypotonia in PWS.

 

Dr. Harold van Bosse, an Orthopedic Surgeon from Shriner's Hospital Philadelphia, discussed the common and challenging problem of scoliosis in PWS.  Scoliosis can start very early in PWS (even in the first year), and has been reported to affect more than 70% of those with PWS by adulthood.  Scoliosis in young children (<4 yo) is generally different than that in older children (10 yo and up), with younger children commonly experiencing a "C-shaped" curve, and older children experiencing an "S-shaped" curve.  It should be noted that early scoliosis is not necessarily predictive of severe scoliosis in young adulthood.  Scoliosis in PWS also has some unusual features compared to “typical” scoliosis.  These differences may include less rotation than typical scoliosis, which can make it harder to detect on the ‘touch your toes’ screening test.  Thus, it’s very important that kids with PWS be followed by X-ray during growth, and Dr. van Bosse suggests monitoring start as soon as a child is sitting independently.  Lordosis at the shoulder and neck, which can make keeping the head up a challenge, is also very common in PWS.  Overall, treatment for scoliosis for those with PWS is similar to the typical population. Parents should encourage activity, particularly to strengthen core muscles (abdomen and back), and physical therapy is helpful.  Casting can be used for young children with a high degree of curvature, and bracing should be considered for children with moderate curvature.  Surgery can be considered later for those with severe scoliosis.  The good news on this front is that the techniques and hardware are improving.  The cautionary tale is that there are PWS-specific issues (including lower bone density, increased pain tolerance, anesthesia and respiratory issues) that need to be carefully considered when determining whether to proceed with surgery as well as what approach to take and what complications to be on the lookout for.  It’s wise to make sure that the surgeon who performs the operation is familiar these PWS-specific issues, or is willing to spend some time learning about them.

Theresa Strong, Chair of FPWR’s Scientific Advisory Board, gave a report on the recommendations from the PWS Research Strategy Workshop, an NIH-sponsored international gathering of scientists to develop a plan for advancing PWS research. The Workshop participants prioritized research questions, identified needed resources and developed specific recommendations to accelerate research. A copy of the "PWS Research Strategy Workshop: Report to the Community" is available, contact Theresa at grants@fpwr.org.

At lunch, Keegan Johnson, President of FPWR-Canada, led a session on “Finding the ‘fun’ in Fundraising”, which, in fact, was pretty fun!  Tanya Johnson, Rachel Johnson and Susan Hedstrom all shared their experiences and tips on bringing a fundraiser together.  Acknowledging that it is the rare person who actually feels comfortable starting to do fundraising, Susan Hedstrom has put together a ‘how to’ guide that she’s happy to share.  As well, there’s safety (and lots of encouragement) in numbers. Thus the chance to join in on the One SMALL Step for Prader-Willi Syndrome international event in the summer of 2011, a multi-site walk in support of the goals of the PWS Workshop, is a fantastic opportunity to jump into fundraising.  More on this initiative will be coming soon, but in the meantime, view a video of this year's walk, here.

Jim Resnick, PhD [Associate Professor of Genetics, University of Florida] has a longstanding interest in understanding how imprinting in the PWS region occurs. He has recently completed an FPWR-sponsored project to make a novel mouse model of PWS, which will allow scientist to use new approaches to understanding the PWS phenotype (characteristics).  Dr. Resnick told the group about the new mouse model.  Previous PWS mouse models had the PWS region disrupted in every cell of the mouse throughout development.  Using some newer techniques available for genetic engineering of mice, Dr. Resnick’s group developed mice with a “conditional knockout’ of the PWS region. They are specifically knocking out the imprinting center (IC) of the PWS region, and have precisely mapped the critical portion of the PWS IC through this model.  In the conditional knockout mice, you can control when during development and in what cells/tissues of the mouse the PWS region gets deleted.  This approach allows scientists to precisely manipulate where and when the PWS defect appears, giving them the opportunity to ask questions that could not otherwise be addressed.  Dr. Resnick is just starting to characterize the mouse, and their initial study has shown that knocking the PWS IC out right away in development gave mice with very similar traits to previously described PWS mice, as expected.  They are now moving on to doing the knockout at various times during development, including before or soon after the brain starts developing. These studies are already starting to yield some interesting findings with respect to how early the PWS IC needs to get knocked out to see an effect.  Overall, it’s expected that these mice will allow Dr. Resnick to pinpoint the critical time for the PWS region genes to be active.  Their group, or other groups who want to use the mice (the mice have already been given to a central repository so other scientists can use them) can also look at questions such as- what happens if the PWS genes are functional in the brain, but not in muscle – are the mice still weak at birth?  These mice should prove very useful in sorting out what time in development, what specific cells in the brain, and what organs in the body are critical to the PWS characteristics.

Elizabeth Roof Elizabeth Roof M.A, L.P.E is a Senior Researcher at the Vanderbilt Kennedy Center. She spoke on Behavior, Development and Family Stress in PWS.  She started out saying that the genes affected in PWS likely change how the hypothalamus works, affecting temperature regulation, eating behavior, sleep, growth, and sex hormones. Additionally various neurochemicals and neuropeptides likely work differently in PWS affecting serotonin, ghrelin and oxytocin, which may be related to difficulties with emotional regulation (rages, outbursts and mood swings).  Food seeking and over-eating often occurs between ages of 2 and 6, but may occur much later.  This is NOT a matter of will power and is caused by a brain dysfunction related to satiety.  Her group did a study where they showed persons with PWS pictures of food (regular food, unusual food combinations and contaminated food).  EEG (brain) studies showed limited or no registration of the “typical” reaction to distasteful food combinations, dirty or germy food. Persons with PWS often know what they should do, but in real situations, impulse takes over and they eat the food they know they should not eat.

In terms of non-food related behavior issues in PWS, Elizabeth listed several areas in which our children struggle such as: asking repetitive questions especially about schedules; hoarding behaviors; having a certain way of doing tasks and often wanting/demanding others to do it this way; a strong need to finish; writing and erasing repeatedly.  In addition, they can be negative/pessimistic and they may hold grudges (often remember negative events more than positive ones).  Studies have shown that the highest number of behavioral problems are seen between ages of 20-29 BUT drop in severity and frequency in mid-adulthood (30-50 y.o)

Ms. Roof stated that their studies have shown that parents of children with PWS experience very high levels of stress (self report and cortisol levels), even higher than parents of other developmentally disabled children.  Our children “wear us out”.  As a result we may have more physical ailments and sleep problems.  In particular, stress was highest among PWS mothers who had a history of anxiety and who used avoidant coping strategies (social withdrawal, denial, not utilizing resources, use of drugs or alcohol to cope).  Our stress also goes up with certain PWS behaviors: compulsive behaviors, verbal perseveration and skin picking.  Their group is conducting studies on the usefulness of parent mentors and support groups, especially groups focused on Mindfulness (Meditation/Breath work, focus on the current moment; movement (e.g., Yoga)).   Results are not out yet but it seems likely these approaches will be helpful. Ms. Roof also suggests that we focus on positive aspects of our child, keep clear on our wishes and dreams vs. the child’s; create a support network and take care of ourselves physically and emotionally.

FPWR Board member Lauren Schwartz Roth provided some extra thoughts from the trenches as a PWS parent and clinical psychologist regarding coping:

- Join a local support group of mothers with special needs children (does not have to be PWS)

- Avoid being an “avoidant coper”.  This seems to lead to significantly greater distress:

Avoidance coping strategies include behavioral or cognitive efforts to keep from thinking about a stressful problem or situation (pretending it is not a problem, pushing away thoughts about the problem, not utilizing resources); Avoidant copers also tend to withdrawal from social support resources, do not ask for help from others, and can get very isolated or feel that “no one really understands”.  Avoidant copers may also rely heavily on alcohol or drugs (prescription or otherwise) to deal with the situation. 

Pro-active copers (who do better in general coping with any kind of illness or trauma in themselves or in a family member) tend to get involved with others in a similar situation; they gather a lot of information about the problem they are facing; they do something active related to their situation; they seek out and ask for help and support.                                                      

Read a more detailed version of Elizabeth's talk, provided by Lauren, here.

Joan Han, MD [Assistant Clinical Investigator, National Institute of Child Health and Human Development, NIH] has recently published a paper with Dr. Andrea Haqq and colleagues, showing for the first time that individuals with PWS have low levels of the neuropeptide brain derived neurotrophic factor (BDNF) in their blood [Han et al, 2009].   Dr. Han initially started studying BDNF in the (really, really) rare disorder, WAGR (a syndrome characterized by Wilm’s tumor, aniridia, genitourinary abnormalities, and mental retardation).  Dr. Han’s group noted that a subset of WAGR syndrome patients experienced hyperphagia, obesity, and additional behavioral challenges.  In a very elegant study, she demonstrated that this subset of patients had a larger deletion on chromosome 11, which included the BDNF gene.  Thus, low levels of BDNF was linked to obesity and cognitive/behavioral issues.   Dr. Han talked more about the BDNF story in the general population (BDNF variant genes result in lower levels of BDNF in some individuals, and those variants are associated with more obesity) as well as her plans to follow up on the initial observation in PWS individuals.  At the NIH, she’ll be looking at BDNF and another pathway important in regulating food intake (MCH) in PWS.  In collaboration with Dr. Haqq at Unviersity of Alberta (see new projects funded by FPWR) she will be supporting studies to examine the cognitive effects of low BDNF in children with PWS.  Encouragingly, Dr. Han’s group is preparing to evaluate a new drug that might act to overcome the BDNF deficiency.  They will do the initial clinical study in the WAGR population, but if it proves safe and effective in those individuals, it may be also applicable to people with PWS. 

Sunday evening provided some relaxed time, with Lauren Schwartz Roth, Ph.D. facilitating, for sharing experiences, strategies and encouragement about raising our children and keeping the entire family healthy and happy.  

 

Monday

Theresa Strong talked about FPWR’s grant program, which has now provided more than $1.6 million to support forty projects.  She provided examples of the outcomes and returns on investment from projects supported in previous years, and gave a brief summary of each of the seven projects FPWR is funding in 2010.  Descriptions of each of the projects is available here.

Andrew Sharp, Ph.D. [Associate Professor of Genetics and Genomic Sciences, Mount Sinai School of Medicine, NYC] is an expert in chromosome structure and epigenetics. He gets a gold star for perseverance - after having his flight cancelled at 1am, he hopped a train from NY to DC at 3am and made it to his 9:00 presentation with 30 minutes to spare.  He must have had a nice, strong cup on coffee on the way, because he gave a very lucid talk on work he has been doing to understand imprinting across the genome and particularly in the PWS region of chromosome 15.  He reviewed recently published work from his laboratory [Sharp et al., 2010] identifying areas near the PWS region that are imprinted, but have not been previously appreciated. His lab developed a novel way to identify and characterize these regions.  The findings are important since these regions may underlie some of the phenotypic differences found between the different subtypes of PWS (UPD vs. deletion), and their identification leads to genetic regions to consider in understanding these differences.  He also spoke about a newly described role for the gene, PRDM9, which may have relevance to understanding how PWS occurs.  Others have shown that PRDM9 is important in the shuffling, or recombination, of genetic material on chromosomes before they are transmitted from parent to child.  Dr. Sharp is investigating whether variants of this protein may put some individuals at higher risk of having a child with a small deletion, as in PWS.  Dr. Sharp’s fascinating work provides a new understanding of imprinting in general and gives some insight into how the PWS might arise.  We look forward to hearing about his continuing studies in this area.

The morning talks were followed by a wonderful day at the Belle Haven Country Club, where a golf and tennis tournament was being held to raise funds for PWS research. The kids swam and had a tennis clinic, while the adults mostly relaxed by the pool.  It was a perfect day for the events, and we were even treated to a bald eagle flying overhead to watch the tournament. 

Many thanks to all the families who traveled from near and far to attend!