This is a competitive renewal application from an inter-institutional group of investigators with long-standing interest in Angelman syndrome (AS), Rett syndrome (RTT), and Prader-Willi syndrome (PWS) to continue a Rare Diseases Clinical Research Center (RDCRC) within the Rare Diseases Clinical Research Network (RDCRN). The Center will focus on these three disorders based on the expectation that the near-term potential for meaningful therapy is strong.
The specific aims for AS are 1) to conduct longitudinal assessments on individuals with AS according to genotype, 2) establish genotype-phenotype correlations based on molecular defect type, and 3) to examine the efficacy of existing therapies including developmental interventions with respect to the genotype-phenotype.
The specific aims for RS will be 1) to establish phenotype/genotype correlations over a broad spectrum of Rett phenotypes, 2) to perform longitudinal studies on an extensive population of individuals with Rett, and 3) to extend the survival study on a broad spectrum of Rett individuals. Recent results from studies in animal models provide a basis for clinical trials in the next 5 years.
The specific aims for PWS are 1) to conduct longitudinal studies according to genotype, 2) to perform natural history studies on non-PWS individuals with early-onset morbid obesity (EMO) and compare them with PWS, and 3) to develop parameters and tool for clnical trials. A pilot project spanning the three disorders will examine the characteristics and patterns of sleep disorders, well-known accompaniments of each (funded by IRSF). The RDCRC will utilize GCRCs in Birmingham, Boston, Gainesville, Houston, Irvine, Kansas City, and Nashville. The Center is expected to function synergistically with the Intellectual and Developmental Disability Center-IDDRC (formerly the MRRC) at UAB. An extensive training program is proposed for stimulating the entry of new investigators into clinical research on rare diseases (funded by IRSF and PWSA). The Center will have active affiliation with the International Rett Syndrome Foundation (IRSF), the Angelman Syndrome Foundation (ASF), and the Prader-Willi Syndrome Association (PWSA). A website for this RDCRC is available at www.circ.uab.edu. This site will be amplified to include a wide range of information for AS, RTT, and PWS.

Public Health Relevance

Effective treatment of Angelman syndrome (AS), Rett syndrome (RTT), and Prader-Willi syndrome (PWS) requires understanding their natural history through longitudinal assessments. We believe more strongly than in the initial proposal that near-term potential for therapy in these disorders is promising. Thus, understanding their common clinical issues disorders (such as nutrition, seizures, sleep and behavior) and the most effective interventions for them are highly relevant.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD061222-10
Application #
8539385
Study Section
Special Emphasis Panel (ZRG1-HOP-Y (50))
Program Officer
Parisi, Melissa
Project Start
2003-09-30
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
10
Fiscal Year
2013
Total Cost
$1,195,553
Indirect Cost
$82,992
Name
University of Alabama Birmingham
Department
Pediatrics
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Percy, Alan K (2016) Progress in Rett Syndrome: from discovery to clinical trials. Wien Med Wochenschr 166:325-32
Killian Jr, John T; Lane, Jane B; Lee, Hye-Seung et al. (2016) Caretaker Quality of Life in Rett Syndrome: Disorder Features and Psychological Predictors. Pediatr Neurol 58:67-74
Sajan, Samin A; Jhangiani, Shalini N; Muzny, Donna M et al. (2016) Enrichment of mutations in chromatin regulators in people with Rett syndrome lacking mutations in MECP2. Genet Med :
Merkel, Peter A; Manion, Michele; Gopal-Srivastava, Rashmi et al. (2016) The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Orphanet J Rare Dis 11:66
Ward, Christopher S; Huang, Teng-Wei; Herrera, José A et al. (2016) Loss of MeCP2 Causes Urological Dysfunction and Contributes to Death by Kidney Failure in Mouse Models of Rett Syndrome. PLoS One 11:e0165550
Neul, Jeffrey L; Sahin, Mustafa (2015) Therapeutic Advances in Autism and Other Neurodevelopmental Disorders. Neurotherapeutics 12:519-20
Peters, Sarika U; Gordon, Reyna L; Key, Alexandra P (2015) Induced gamma oscillations differentiate familiar and novel voices in children with MECP2 duplication and Rett syndromes. J Child Neurol 30:145-52
Neul, Jeffrey L; Glaze, Daniel G; Percy, Alan K et al. (2015) Improving Treatment Trial Outcomes for Rett Syndrome: The Development of Rett-specific Anchors for the Clinical Global Impression Scale. J Child Neurol 30:1743-8
Butler, Merlin G; Wang, Kun; Marshall, Jan D et al. (2015) Coding and noncoding expression patterns associated with rare obesity-related disorders: Prader-Willi and Alström syndromes. Adv Genomics Genet 2015:53-75
Pozzo-Miller, Lucas; Pati, Sandipan; Percy, Alan K (2015) Rett Syndrome: Reaching for Clinical Trials. Neurotherapeutics 12:631-40

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