AURORA, Ill.—The Angelman Syndrome Foundation (ASF) has announced its 2014 call for research proposals, planning to award up to $1 million in support of Angelman syndrome (AS) research.
One- or two-year grants will be awarded for amounts of up to $100,000-per-year to promising preclinical, translational or clinical research areas that investigate all aspects of AS. Highest priority will be given to pilot projects to test new ideas about pathogenesis and therapeutics. Researchers from all countries are encouraged to apply. Applications are due October 15.
AS is a neuro-genetic disorder characterized by severe intellectual and developmental disability, sleep disturbance, seizures, jerky movements (especially hand-flapping) and frequent laughter or smiling. AS is a classic example of genomic imprinting in that it is caused by deletion or inactivation of genes on the maternally inherited chromosome 15 while the paternal copy, which may be of normal sequence, is imprinted and therefore silenced. This large chromosome deletion is the most common mechanism and occurs in 68 percent of all individuals with the syndrome. Because the UBE3A gene has been removed, there is deficient expression of it in the brain and AS results.
This deletion can be screened for by the DNA methylation test, typically performed on a blood sample. Confirmation of the deletion however requires the fluorescence in situ hybridization (FISH) test or a molecular chromosome study.
Individuals with AS are quite animated in their attempts at communication and can be pro-social even though they have severe speech impairment. Although fluent sign language is beyond the motor and cognitive abilities of those with AS, there is an important type of gesturing communication that occurs by more simplistic physical signals that are less complicated than formal sign language. As one example of the foundation’s activities, it has funded a project to gain information about how to use, and build upon, the natural gesturing capabilities of those with AS.
Severe seizure problems in AS can limit developmental outcomes and disrupt family life. In those with the most severe seizures, the chromosomal deletion also removes an adjacent gene, GABRB3, important in regulating the membrane sensitivity of the neuron. It was hoped that developing a mouse model with GABRB3 deleted would provide more information about epilepsy and EEG patterns in AS. This foundation-funded work has helped clarify the primary and major role of UBE3A disruption in causing seizures in AS.
ASF-funded research is currently making great progress using antisense oligonucleotides drugs and the foundation believes that a Phase 1 clinical trial may be within striking distance.
To date, the ASF has invested more than $6 million in AS research, supporting 78 projects worldwide.