Prader-Willi Syndrome Research Update
For the 2007 Research Update on Prader-Willi syndrome , please click here .
2006 PRADER-WILLI SYNDROME RESEARCH UPDATE
This year has been an exciting one for PWS research. Like many areas of medical research, Prader-Willi research studies have benefited from a number of new technologies. From the ability to screen expression of tens of thousands of genes at one time on a microchip, to the development of advanced noninvasive techniques for visualizing the brain at work, these new techniques are allowing medical research to advance at an unprecedented pace. Coupled with some insightful questions and old fashioned hard work, these techniques have led to a better understanding of the changes associated with PWS, opening new doors to understanding and treating Prader-Wili Syndrome .
Exciting Updates in the Research Arena
This year saw the first understanding of how disruption of special "snoRNAs" (small nucleolar RNAs) in the PWS region of chromosome 15 affects the function of other genes (1). Specifically, loss of one particular snoRNA in the PWS region leads to an alteration in the serotonin system - a system that regulates appetite, mood and sleep, among other things. Thus, the molecular ‘reasons' for the PWS characteristics are beginning to come to light. The PWS field continues to benefit from intense efforts to understand appetite regulation, just as the field of obesity research has benefited from studying the special case of PWS. The past few years have seen the discovery of several new molecules critical to appetite control in typical individuals as well as those with PWS. These include leptin, a signal of ‘fullness;' orexin, a peptide important in both appetite control and wakefulness (which is abnormally low in some with PWS;) and ghrelin, the hunger molecule that is abnormally high in those with PWS. While past years have focused on identification and initial characterization of these ‘hunger hormones,' this year has been marked by advances in understanding how these signals are integrated in the brain to control food intake, influence the reward circuitry (emotions,) and regulate energy expenditure. An understanding of the integration of these signals will be critical for development of effective, hunger-curbing drugs.
Overview of Projects Funded in 2006
In 2006, the strong support of our donors and members allowed FPWR to support a wide range of research projects to further stimulate the field. Five projects were approved for funding in 2006, ranging from a basic study to understand what goes wrong at the molecular level (Stamm) to a clinical evaluation designed to help kids with PWS be successful learners (Olley), and several points in between. A brief description of the FPWR supported projects, each of which addresses a critical area of PWS research, is listed below:
1. snoRNAs LOCATED IN THE PWS CRITICAL REGION REGULATE ALTERNATIVE SPLICING OF PRE-mRNAs. Stefan Stamm, Ph.D., University of Erlangen, Germany ($40,000 in 2006). Dr. Stamm recently published an exciting paper in Science describing how the genetic defect in PWS leads to disruption of the serotonin 2C receptor, which may alter the serotonin system in the brain. In the current proposal, Dr. Stamm will follow up on those studies, examining other genes that may be altered due to the loss of chromosome 15 material. These studies will help us understand the underlying problem in PWS and may identify new therapeutic targets.
2. LINKING LEARNING WITH NEURODEVELOPMENTAL FUNCTIONING: MANAGEMENT STRATEGIES FOR CHILDREN WITH PRADER-WILLI SYNDROME. J. Greg Olley, Ph.D., Children's Center for Development and Learning, University of North Carolina-Chapel Hill ($40,000 in 2006). Dr. Olley and his team work with Dr. Mel Levine, who has advanced a very popular neurodevelopmental model of learning for people with learning differences (http://www.allkindsofminds.org). In this project, Dr. Levine's model will be applied to children with PWS. Strengths and needs will be assessed, and a model of learning specific to PWS will be linked to optimized learning strategies, providing parents and teachers with practical tools to improve learning for people with PWS.
3. REGULATION OF EXPRESSION OF PRADER-WILLI SYNDROME REGION GENES IN THE HYPOTHALAMUS BY NUTRITIONAL AND HORMONAL SIGNALS. Stephen O'Rahilly, Ph.D., University of Cambridge ($40,000 in 2006). Dr. O'Rahilly is a leading scientist in the field of hunger regulation, obesity and energy balance. His group recently determined that genes in the PWS region are regulated by nutritional and hormonal signals detected by the hypothalamus. In this project, they will determine how these signals influence expression of PWS-region genes, and evaluate approaches to manipulate this interaction.
4. THE SYMPATHETIC AND ENTERIC NERVOUS SYSTEMS IN NECDIN-NULL MICE. Rachel Wevrick, Ph.D., University of Alberta, Canada ($40,000 for 2006) Necdin is one of the genes on chromosome 15 that is not expressed in those with PWS. Dr. Wevrick has shown that necdin is important in directing the normal growth of neurons. Here she will study how loss of the necdin gene affects innervation of the gastrointestinal tract and the function of the autonomic nervous system.
5. EVALUATION OF SENSORY PROCESSING IN INDIVIDUALS WITH PWS. Lucy Jane Miller, Ph.D., OTR, KID Foundation and University of Colorado ($40,000). Dr. Miller, a leading authority on sensory processing disorder (SPD), will study the ability of children with PWS to regulate sensory stimuli from the environment. This study will define whether SPD contributes to the characteristics of PWS, and may suggest new therapeutic interventions.
(1) Kishore S, Stamm S. The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C. Science 311:320, 2006.
For more information on how FPWR conducts research, please review our research objectives or review a list of all grants that FPWR has funded to date.
2006 PRADER-WILLI SYNDROME RESEARCH UPDATE
This year has been an exciting one for PWS research. Like many areas of medical research, Prader-Willi research studies have benefited from a number of new technologies. From the ability to screen expression of tens of thousands of genes at one time on a microchip, to the development of advanced noninvasive techniques for visualizing the brain at work, these new techniques are allowing medical research to advance at an unprecedented pace. Coupled with some insightful questions and old fashioned hard work, these techniques have led to a better understanding of the changes associated with PWS, opening new doors to understanding and treating Prader-Wili Syndrome .
Exciting Updates in the Research Arena
This year saw the first understanding of how disruption of special "snoRNAs" (small nucleolar RNAs) in the PWS region of chromosome 15 affects the function of other genes (1). Specifically, loss of one particular snoRNA in the PWS region leads to an alteration in the serotonin system - a system that regulates appetite, mood and sleep, among other things. Thus, the molecular ‘reasons' for the PWS characteristics are beginning to come to light. The PWS field continues to benefit from intense efforts to understand appetite regulation, just as the field of obesity research has benefited from studying the special case of PWS. The past few years have seen the discovery of several new molecules critical to appetite control in typical individuals as well as those with PWS. These include leptin, a signal of ‘fullness;' orexin, a peptide important in both appetite control and wakefulness (which is abnormally low in some with PWS;) and ghrelin, the hunger molecule that is abnormally high in those with PWS. While past years have focused on identification and initial characterization of these ‘hunger hormones,' this year has been marked by advances in understanding how these signals are integrated in the brain to control food intake, influence the reward circuitry (emotions,) and regulate energy expenditure. An understanding of the integration of these signals will be critical for development of effective, hunger-curbing drugs.
Overview of Projects Funded in 2006
In 2006, the strong support of our donors and members allowed FPWR to support a wide range of research projects to further stimulate the field. Five projects were approved for funding in 2006, ranging from a basic study to understand what goes wrong at the molecular level (Stamm) to a clinical evaluation designed to help kids with PWS be successful learners (Olley), and several points in between. A brief description of the FPWR supported projects, each of which addresses a critical area of PWS research, is listed below:
1. snoRNAs LOCATED IN THE PWS CRITICAL REGION REGULATE ALTERNATIVE SPLICING OF PRE-mRNAs. Stefan Stamm, Ph.D., University of Erlangen, Germany ($40,000 in 2006). Dr. Stamm recently published an exciting paper in Science describing how the genetic defect in PWS leads to disruption of the serotonin 2C receptor, which may alter the serotonin system in the brain. In the current proposal, Dr. Stamm will follow up on those studies, examining other genes that may be altered due to the loss of chromosome 15 material. These studies will help us understand the underlying problem in PWS and may identify new therapeutic targets.
2. LINKING LEARNING WITH NEURODEVELOPMENTAL FUNCTIONING: MANAGEMENT STRATEGIES FOR CHILDREN WITH PRADER-WILLI SYNDROME. J. Greg Olley, Ph.D., Children's Center for Development and Learning, University of North Carolina-Chapel Hill ($40,000 in 2006). Dr. Olley and his team work with Dr. Mel Levine, who has advanced a very popular neurodevelopmental model of learning for people with learning differences (http://www.allkindsofminds.org). In this project, Dr. Levine's model will be applied to children with PWS. Strengths and needs will be assessed, and a model of learning specific to PWS will be linked to optimized learning strategies, providing parents and teachers with practical tools to improve learning for people with PWS.
3. REGULATION OF EXPRESSION OF PRADER-WILLI SYNDROME REGION GENES IN THE HYPOTHALAMUS BY NUTRITIONAL AND HORMONAL SIGNALS. Stephen O'Rahilly, Ph.D., University of Cambridge ($40,000 in 2006). Dr. O'Rahilly is a leading scientist in the field of hunger regulation, obesity and energy balance. His group recently determined that genes in the PWS region are regulated by nutritional and hormonal signals detected by the hypothalamus. In this project, they will determine how these signals influence expression of PWS-region genes, and evaluate approaches to manipulate this interaction.
4. THE SYMPATHETIC AND ENTERIC NERVOUS SYSTEMS IN NECDIN-NULL MICE. Rachel Wevrick, Ph.D., University of Alberta, Canada ($40,000 for 2006) Necdin is one of the genes on chromosome 15 that is not expressed in those with PWS. Dr. Wevrick has shown that necdin is important in directing the normal growth of neurons. Here she will study how loss of the necdin gene affects innervation of the gastrointestinal tract and the function of the autonomic nervous system.
5. EVALUATION OF SENSORY PROCESSING IN INDIVIDUALS WITH PWS. Lucy Jane Miller, Ph.D., OTR, KID Foundation and University of Colorado ($40,000). Dr. Miller, a leading authority on sensory processing disorder (SPD), will study the ability of children with PWS to regulate sensory stimuli from the environment. This study will define whether SPD contributes to the characteristics of PWS, and may suggest new therapeutic interventions.
(1) Kishore S, Stamm S. The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C. Science 311:320, 2006.
For more information on how FPWR conducts research, please review our research objectives or review a list of all grants that FPWR has funded to date.
