About Angelman syndrome (AS)
Angelman syndrome (AS) is a rare neurogenetic disorder that affects about one in 15,000 people, or approximately 500,000 individuals worldwide. People living with AS have a genetic difference on chromosome 15 that affects the UBE3A gene and as a result, they do not make enough functional UBE3A protein.
The UBE3A gene is unusual in that it is imprinted, meaning that the expression of the gene depends on whether the gene is on the maternal or paternal chromosome 15. In the brain, the paternal UBE3A gene is silenced, so all UBE3A protein in the brain comes from the maternal UBE3A gene. The UBE3A protein is a ubiquitin ligase, involved in ubiquitination, a key process in regulating protein abundance and function within the brain. UBE3A is also involved in gene regulation. In the absence of UBE3A, communication between neurons is impaired and regulation of many other brain proteins is affected.
Angelman syndrome is always caused by not making enough UBE3A in the brain. There are five underlying genetic mechanisms, commonly called genotypes, in AS: maternal deletion of chromosome 15q11.2-q13 (includes the UBE3A gene), paternal uniparental disomy (UPD) of chromosome 15, mutation within the UBE3A gene, imprinting center defect (ICD) affecting the expression of maternal UBE3A, and mosaicism for one of the above.
Clinical Features of our Community
Features of Angelman syndrome often become apparent during the first year of life. Most babies living with Angelman syndrome have a typical pregnancy and typical birth with no major birth defects. Developmental delays are typically noticeable by 6-12 months of age. Babies living with AS may have hypotonia, difficulty feeding, and hypopigmentation (pale eye and skin color compared to family background).
Most children and adults living with AS have some or all of the following characteristics: Movement or balance difficulties, resulting in difficulties walking and using the hands;  Severe speech impairment, with limited to no use of words; Receptive language (understanding what is said) and nonverbal communication (using gestures) abilities that are often better than their speaking ability;  Unique behaviors, including frequent laughter and smiling, an apparently happy demeanor, excitability, hand-flapping, short attention span, or excessive movement (hypermotoric);  Neurodevelopmental delays.
It is also common for a child or adult living with Angelman syndrome to have:  Slower head growth, which may result in a small head size compared to their body size;  Seizures, usually starting before age 3; Chewing and mouthing behaviors;  Difficulty with eye muscle control, causing lazy eye or eye crossing (strabismus);  Fascination or obsession with water;  Walking with a wide-based gait and ankles turning out;   Scoliosis (curving of the spine);  Constipation (difficulty with bowel movements); Difficulties sleeping with disrupted sleep and abnormal sleep-wake cycles.
Our Mission
FAST was founded in 2008 by an all-volunteer board of AS parents. FAST is based in the USA but leads a network of country and region-based allies. FAST quickly adopted a business model based on assessing the landscape of potential research areas related to AS; seeding that landscape through generous grants; and, if and when lightning struck, shepherding new insights or technologies from the academic space to the pharmaceutical one—all the while maintaining input and control over the direction of the research.
With the support of a generous community and leadership by savvy and scientist parents and collaborators, FAST has backed multiple proof-of-concept products all the way to human drug candidates, one of which is now in phase 3 clinical trials. FAST continues to support a variety of drug development programs as well as projects like endpoint and biomarker development that provide the foundation for clinical trials. FAST maintains an all AS parent board of directors, leading FAST forward, while a stellar paid team and amazing volunteers work to achieve the set goals.
With technology advancing at a rapid pace, FAST focuses on every possibility for Angelman syndrome (cureangelman.org/current-pipeline for more information). FAST is committed to ensuring that all programs reach the right inflection point to know if each has a clear path forward. It’s our job to chase down every possible option for transformative treatments, and to filter out the absolute best ones for everyone around the world living with AS—regardless of genotype, and regardless of age.
Our Mission is to cure Angelman syndrome.
I am Especially Proud of...
FAST is the largest non-governmental funder of Angelman syndrome research in the world. We are proud that we set the agenda for the therapeutic landscape for AS. We accelerate that agenda, from funding promising research at the academic level all the way to starting companies and creating the necessary infrastructure outside of drugs and their development. Along the way, we activate and educate those in the worldwide AS community, to support all the work required for drug development.
Excited to REN Because...
Angelman syndrome is caused by the lack of a specific protein, UBE3A, in the brain. Many features of AS overlap with other neurodevelopmental conditions, and a substantial portion of individuals who were previously diagnosed clinically with AS are now known to have a different genetic condition that is one of our partners here at REN! Building a network with other organizations enables us to better serve all families affected by rare epilepsies. Lessons learned from AS research-- about the brain, UBE3A function, and downstream effects-- are applicable to many other REN conditions. And likewise, learnings from the other conditions affecting the same or similar pathways will be beneficial to FAST and Angelman syndrome research. Moreover, REN has developed so many tools and partnerships. Collaborating increases efficiency, amplifies our voices, and makes us all more powerful.
My Journey and Motivation...
On January 7, 2020, our first-born son, William, was diagnosed with Angelman syndrome, at 2.5 years old. Finally, we have an answer to his developmental delays, but now what? We quickly found FAST and the Angelman syndrome community. We channeled our grief by joining others around the world to use our time and talent to help bring a meaningful treatment to William and all others living with AS.
Today, as both an AS parent and as the director of public engagement for FAST, my motivation is fueled by the passion, commitment, and persistence of this community – our board, staff, academic and industry partners, and most of all, families and caregivers around the world. Being part of a rare disorder presents unique challenges and forces us to find creative ways to be seen and heard, in order to make progress. We have come incredibly far and FAST (pun intended) yet there will remain a collective fight until an approved therapeutic is accessible for our loved ones.
By Niki Armstrong, VP Genetic Services & Education & Meghan Edberg, Director of Public Engagement