Communication/Educational Programs For Students With Angelman Syndrome In Inclusive Classrooms: A Look At Best Practices

Dr. Stephen Calculator, University of New Hampshire, Durham, NH

One of the problems in obtaining optimal educational services for children with AS is that there is not much information regarding placement in inclusive classrooms and in other settings. What can we learn from parents and teachers about their reactions to certain educational placements?  This work by Dr. Calculator involved interviews and additional study of selected families and has helped provide the AS community with this information.

Genetic Dissection Of The Molecular Pathways Underlying The Pathogenesis Of Angelman Syndrome

Dr. Fen-Biao Gao, J. David Gladstone Institute, San Francisco, CA

This scientist performed studies on Drosophila, the fruit fly, to determine how UBE3A dosage affects neuron development. The results demonstrated that synaptic connections and dendritic processes are abnormal both when the UBE3A protein is in high and in low amounts. This work helped focus efforts on UBE3A research to the neuron’s synaptic region in the hopes of gaining new insight about how UBE3A is important for normal brain development. This work in combination with previous funding to other investigators (see above for the 2000, Ethan Bier, grant) established the usefulness of the fruit fly as another important experimental model in the study of AS.

Investigation Of The Role Of UBE3A In Synapse Development

Dr. Michael Greenberg, Children’s Hospital Boston , Boston, MA

We know that UBE3A action inside brain cells is extremely complicated but the research of Dr. Greenberg and his lab has greatly helped to dissect and better understand this complexity. Using mouse models and using powerful genetic technologies to study individual neuron cells, their lab identified new protein targets that regulate synaptic development and activity. Importantly, these new proteins are related to other proteins for which druggable targets have been established and this area of research is creating new ideas about possible new pharmaceutical or other novel types of treatment approaches.

Facial Phenotype-Genotype Correlations In Angelman Syndrome

Dr. Peter Hammond, UCL Eastman Dental Institute, London UK

Is there a characteristic or noteworthy facial appearance of individuals with AS?  Certainly it is known that those with AS have facial characteristics reflecting the normal traits of their parents but are there subtleties that might lead to an earlier or more accurate diagnosis of the syndrome especially in those for whom genetic testing has not confirmed any abnormality. This work used advanced three-dimensional surface morphology studies and powerful computer analysis to analyze surface modeling of the face in those with AS.

Elucidating The Function Of The E6AP Ligase At Mammalian CNS Synapses

Dr. Gentry Patrick, University of California, San Diego, San Diego, CA

Work from this grant was part of several projects funded by ASF in order to learn more about UBE3A and its relationship to the larger, complex system of protein degradation (called the ubiquitin-proteasome pathway) that is important to all cellular function. Dr. Patrick’s project helped delineate the action of UBE3A-like enzymes in this complex protein degradation pathway.

Effects Of Premature Truncation Of The UBE3A Antisense transcript On UBE3A Imprinted Expression

Dr. Lowell Rayburn, Carolinas Medical Center, Charlotte, NC

This grant continued ASF funding to one of the premier AS scientists, Dr. Joe Wagstaff, and his laboratory. The aim of this project was a bold attempt to create therapeutic effects in the mouse model by genetically engineering a control element of UBE3A expression. This element was modified by advanced methods of genetic engineering and embryonic cell treatment. During the course of the study Dr. Wagstaff unfortunately died and this project was discontinued due to the closure of his laboratory and the funds for it returned to the foundation. Dr. Wagstaff was subsequently honored by ASF as an outstanding investigator and ASF now provides grant funding opportunities to young science investigators through the Wagstaff Fellowship program.

Electrogastrography in Children with Angelman Syndrome

Dr. Benjamin Enav, MD, University of California, Los Angeles, California

This study evaluated individuals with AS to learn more about contractility of the stomach as measured by surface electrical recordings from the abdominal area. The study provides insight into how the stomach contracts before, during and after ingestion of meals and the varied gastrointestinal problems known to exist in AS. One of the findings demonstrated increased periods of diminished or absent stomach contractions (termed “arrhythmias”) when compared to controls. This diminished activity may be fundamentally related to the problem of neuronal imprinting of UBE3A not only in the brain but in other neurons in the peripheral nervous system.

Alphabet Therapy: A Novel Way to Teach Children With Angelman Syndrome and Measure Their Academic Abilities

Terry Jo Bichelle, RN, CNM, MPH, Vanderbilt University, Nashville, Tennessee

Individuals with AS lack expressive speech and they have difficulty in understanding the structure and complexity of language. This grant provided funding for a project combining intensive behavioral analysis in combination with visual prompts of alphabet letters, numbers, colors and shapes. This project is one of several funded by ASF that affirms the ability of Angelman children to learn when afforded sufficient resources and targeted strategies of instruction.