Accelerating Into The Future

Scientific Roundtable Discussion Weekend

 By Janalee Heinemann

       PWSA(USA) and our Research Advocacy Team, chaired by Jim Kane, sponsored and coordinated a two-day November meeting in Baltimore where some of the finest minds in PWS research discussed the issue of hyperphagia (uncontrollable appetite). The theme was “Accelerate the Future,” defined by Jim Kane as “bringing to fruition today that progress which otherwise might be a long time coming.”

      The weekend was an opportunity to share current knowledge, discuss ways to move forward in understanding the issues, identify crucial questions in hyperphagia-related research, and plan for new research on hyperphagia. 

      Researchers attended from the USA, United Kingdom and The Netherlands. All have specific experience in appetite control and metabolic problems with diverse backgrounds in genetics, molecular genetics, endocrinology, neurobiology, neuro-imaging, gastroenterology, psychiatry, and nutrition. A representative from the National Institutes of Health (NIH) also attended.  

      The resulting Strategic Plan for Research, to be presented to the PWSA(USA) Board in January, focuses the energy of PWSA(USA) using a new model and a narrow focus to make progress on PWS research at a pace never before seen. The new model emphasizes more collaboration among the scientific group, sources of funding and PWSA. Jim believes the narrow focus will put the right people in the right places with the right support to work on cutting-edge questions.  

      Here are some of the issues that I think you will find interesting.

* Why a focus on hyperphagia?

            • Because it is the controlling force in PWS
            • It is a causative factor in aberrant behavior
            • It prevents our children from becoming independent
            • PWS is a window into the “House of Obesity” 
            • There is commercial and federal potential in funding

* Exploring the phases of PWS identified more than the two phases traditionally reported. Children with PWS often become overweight at 1 ½ to 3 years even without an increase in calories — before the hyperphagia sets in, which can start from 3-12 years. Some adults with PWS who are 30-40 years old have been reported to have a reduction in the tremendous drive to eat. Furthermore, problems which manifest themselves in the newborn infant as “failure to thrive” most likely begin months prior to actual birth. The changes seen in early childhood — from failure to thrive, to normalcy, to thriving too well, to the raging appetite — are intriguing to scientists, presenting many opportunities for study. 

*  Diet:  Adults with PWS typically must be on 800-1200 calories per day, unless on growth hormone, and thus need multivitamin and mineral supplements. They also need adequate fluids and fiber to avoid constipation, due to weak muscle tone. We need to know how to treat diet better if the person has been on growth hormone. What has GH done to the energy-balance equation?

*  Curiously, there are fewer instances of type 2 diabetes than expected for weight and less high fat levels in the blood than expected. Why?

*  Many families are intrigued by surgical options for treatment of severe obesity, from gastric bypass surgery to experimental use of electric stimulators in the stomach area. There has been limited investigation into their application in people with PWS. We hope to learn from bypass surgery being done in Italy and are considering ways to instigate projects in the U.S.       

* Abnormalities in the brain, particularly the hypothalamus, may lead to increased appetite in PWS, such as fewer oxytocin neurons (that inhibit eating) in PWS than controls.  We need a more centralized approach and collaboration for the use and distribution of brain tissue for research since it is so difficult to get.  Deep brain stimulation is being tried in some other brain diseases — the problem is where to position such stimulation  in the brain of those with PWS.

*  Genetic research has identified two major causes of PWS, deletion (types I and II) and uniparental disomy.  Each one has variations such as in behavior and visual memory. What variations exist between the different genetic types in appetite and metabolic problems?

*  Drugs: Ghrelin is the only gut hormone that increases appetite, but high ghrelin levels in PWS are not the whole story. It is unclear whether low levels of other gut and pancreatic hormones that lower appetite contribute to increased appetite in PWS. These hormones can be given to patients or lowered by other drugs (e.g. intra-nasal PYY3-36, somatostatin analogues to lower ghrelin levels) to try and treat the appetite in PWS. However, the PWS brain may not respond normally.  Would other drugs in varying degrees of development to treat obesity in the general population (e.g. those affecting the neuropeptide Y, melanocortin and other  brain receptors; drugs to increase metabolism to burn off energy), be effective in PWS? 

* The European Union (14 countries) recently commissioned establishing a centralized database project for people with PWS.  Several U.S. institutions are setting up a database through a collaborative grant from NIH for rare disorders, a project involving the collection of extensive verified data on a limited number of individuals with PWS.

      Meanwhile, PWSA(USA) is setting up an extensive database for the collection of basic information on as many people with PWS as possible. Each of these data collection efforts promises to build excellent sources of information on PWS for the research community.

       One major problem is a serious lack of geneticists currently being trained. With early diagnosis, we have had a great insurgence of babies now diagnosed with PWS — but who is going to care for our children? 

      The Roundtable Weekend, the first such gathering tailored to a discussion of PWS and the raging appetite and metabolic factors, was considered a success by all who attended.

      Our thanks to the Maryland Private Foundation for providing a portion of the funding for this Roundtable.