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 RTT 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. In addition, evidence emerging from the proposed pilot study on sleep dysfunction in the three disorders should provide the basis for a clinical trial on sleep in RTT. The RTT component sites include UAB, Children's Hospital Boston, Greenwood Genetic Center, and Baylor College of Medicine. GCRCs will be utlized in Birmingham, Boston, and Houston. The travel clinics in Oakland, Chicago, New Brunswick, and Miami will continue to provide geographic diversity for study participants. The Center is expected to function synergistically with the Intellectual and Developmental Disability Center-IDDRC (formerly the MRRC) at UAB, Children's Hospital Boston, and Baylor. 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 RTT sites will have active affiliation with the International Rett Syndrome Foundation (IRSF). A website for this RDCRC is available at www.circ.uab.edu. This site will be amplified to include a wide range of information on all three disorders.

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 #
8539394
Study Section
Special Emphasis Panel (ZRG1-HOP-Y)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
10
Fiscal Year
2013
Total Cost
$34,789
Indirect Cost
$3,121
Name
University of Alabama Birmingham
Department
Type
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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