ASA Annual Report 2025 Is Here
Link to the report We’re proud to share the Angelman Syndrome Alliance’s Annual Report 2025 — “Together for Science and Hope.” This year reflected the
July 3, 2026
Angelman Syndrome Alliance (ASA), a partnership of organizations from around the world that are focused on supporting people with Angelman Syndrome (AS) with our mission to advance groundbreaking research.
By pooling our resources, we can collectively tackle the high costs of research. Identifying the most promising projects is a complex task that our independent Scientific Advisory Board expertly handles. As a non-commercial organization, ASA ensures that our decisions are objective and focused on driving meaningful progress.
Link to the report We’re proud to share the Angelman Syndrome Alliance’s Annual Report 2025 — “Together for Science and Hope.” This year reflected the
The Angelman Syndrome Alliance (ASA) is proud to announce the recipients of its 2026 Scientific Research Grants. This year’s call for proposals attracted exceptionally high-quality
The ASA Members Meeting in Hamburg brought together representatives from across Europe and beyond to reflect on progress and plan ahead. Members confirmed over €270,000
The total funds invested in Angelman Syndrome research programs is 1.800.000,-€.
ASA funded scientific publications
The total amount of members accross the globe are 18 members.
Bringing the top researchers together to exchange ideas and results.
The Angelman Syndrome Alliance (ASA) is dedicated to improving the lives of individuals affected by Angelman Syndrome through collaboration, research, and support. Founded as a coalition of organizations worldwide, ASA aims to advance scientific understanding and develop effective therapies. By pooling resources, the Alliance funds significant research projects and fosters lasting changes in treatment approaches. Our commitment extends to raising awareness, providing educational resources, and offering support to families and caregivers, ensuring a comprehensive approach to tackling the challenges associated with Angelman Syndrome.
The members contribute funds to the research grants provided by the Angelman Syndrome Alliance. Many other organisations attend our annual meetings and contribute through suggestions and guidance. Please do get in contact if you are interested in membership.
Parent organizations that want to become a full member but do not have the necessary means yet, are welcome as Associate members. As an associate you inform interested parties in your country about ASA projects (AS parents, therapists, doctors and scientist ), you to make a list of all important Angelman Syndrome researchers in your country and send it to the scientific board of ASA, and you make a noticeable effort to gather funding so you can participate as a full ASA member. In every country there can be only one parent organization as a representant within ASA.
Hosted by Angelman Japan
Hosted by Angelman UK
Hosted by Austrian Angelman Research Association with Prof. Harald Sitte (Meduni Wien)
Hosted by Angelman e.V.
Hosted by Angelman Portugal
Hosted by Angelman UK
Hosted by French Angelman Syndrome Association (AFSA)
Hosted by ORSA
Hosted by Nina Foundation
The Angelman Syndrome Alliance (ASA) is proud to announce the recipients of its 2026 Scientific Research Grants.
Prof. Ype Elgersma
Project: Understanding UBE3A Protein Homeostasis: Controlling UBE3A Protein Levels in the Brain
Dr. Carmen De Caro
Project: From Diet to Brain: Food Supplementation and Microbiota-Linked Biomarkers in Angelman Syndrome (AS)
Prof. Ben Philpot
Project: Development of Next-Generation, Peripherally-Administered ASOs to Improve Safety and Biodistribution for the Treatment of Angelman Syndrome
| Grant year | Investigators | Project title | Status | Publications | Funding ASA |
|---|---|---|---|---|---|
| 2021 | Ilaria Tonazzini, Laura Baroncelli & Roberta Battini | Innovative brain-targeting nano-tools and imaging methods for therapeutic development in AS | Manuscripts published Interim reports received | Ilaria Tonazzini 2 manuscripts since 2021 Laura 1 manuscript (this study) | 170000 € |
| 2021 | Simao da Rocha & Evguenia Bekman | Stem cell toolkit for modelling cerebella dysfunction in Angelman syndrome | Manuscripts published Interim reports received | Simao da Rocha 2 manuscripts since 2021 Evgenia Bekman 2 manuscripts since 2021 | 170000 € |
| 2019 | Ugo Mayor | Molecular mechanisms of Angelman Syndrome | Completed Final report received Manuscripts published | 3 manuscripts since 2019 | 175000 € |
| 2019 | Ype Elgersma | The role of UBE3A in gene regulation in relation to AS | Completed Final report received Manuscripts published | Ype Elgersma: 32 manuscripts on AS published since 2014 | 100000 € |
| 2019 | Ben Philpot | Quantifying sleep spindles from overnight EEGs as an Angelman syndrome biomarker | Completed Final report received Manuscripts published | 60000 € | |
| 2016 | Ben Philpot | Quantifying EEG abnormalities and identifying biomarkers in Angelman Syndrome | Completed Final report received Manuscripts published | 21 manuscripts since 2016 | 137500 € |
| 2016 | Silvia Russo & Tiziana Borsello | Potential therapeutic approach for synaptic deficit in Angelman syndrome: the JNK inhibitor peptide | Completed Final report received Manuscripts published | Silvia Russo: 2 publications since 2016 Tiziana Borsello: 1 publication (this study) | 135000 € |
| 2014 | Ben Distel | Elucidating the molecular mechanisms underlying E6AP function in the brain | Completed Final report received Manuscripts published | 11 manuscripts on AS since 2014 | |
| 2014 | Geeske van Woerden & Ype Elgersma | In vivo characterisation of E6AP interacting proteins | Completed Final report received Manuscripts published | Ype Elgersma: 32 manuscripts on AS published since 2014 Geeske van Woerden: 12 manuscripts on AS published since 2014 |
The Angelman Syndrome Alliance (ASA) is excited to announce the 2024 Grant Calls winners.
They will be researching the following topics funded by ASA:
“Innovative brain-targeting nano-tools and imaging methods for therapeutic development in Angelman Syndrome (InnovAS)”
The goal of the InnovAS project is to improve future therapeutic pipelines for Angelman Syndrome (AS) by;
Working on a less invasive method to deliver antisense oligonucleotides (ASOs) to the brain, compared to intrathecal injections. The proposed brain-delivery strategy for ASOs targeting Ube3a, will be based on biocompatible nanoparticles that can be delivered non-invasively via intranasal administration.
Assess non-invasive imaging methods as an unbiased biomarker for monitoring brain function in AS.
“Stem cell toolkit for modelling cerebellar dysfunction in Angelman Syndrome”
This research project will investigate the hypothesis that cerebellar dysfunction significantly influences the symptoms of AS, particularly ataxia. In a stem cell-based approach, cerebellar organoids will be generated using novel induced pluripotent stem cells (iPSCs) from patients and genetically matched controls. These “cerebellum-in-a-dish” models will help future drug discovery efforts to improve the lives of patients with Angelman syndrome.
Dr. Ype Elgersma postulates that UBE3A plays a major role in the regulation of gene expression and sets out to identify respective genes. Department of Neuroscience – ERASMUS MC
Dr. Ben Philpot finetunes his last discovery by looking at quantifying sleep spindles from overnight EEGs as an Angelman syndrome biomarker. Associate Director of the UNC Neuroscience Center – UNC-Chapel Hill
Dr. Ugo Mayor has a daring and novel approach to identify and validate the substrates and cofactors (including DUB enzymes) of UBE3A and to test the viability of targeting DUB enzymes as a therapeutic strategy for AS. That intrigued both scientific board as well as the international alliance of parent organizations (Angelman Syndrome Alliance – ASA). Department of Biochemistry @ University of the Basque Country UPV/EHU
“Potential therapeutic approach for synaptic deficit in Angelman syndrome: the JNK inhibitor peptide”
Recent studies have demonstrated that neurons of patients with Angelman syndrome do not work well. AS neurons show defects (deficit at the synapses) that do not allow them to communicate each other and this is at the basis of cognitive deficit in patients. In neurons of Angelman patients, special structures, called synapses, have an alterated shape and work bad. The synapses are crucial for learning, memory and cognitive functions. We want to study the mechanisms which cause this alterations in Angelman animal (mice) and human models . Partner Russo is preparing human models from patients’ blood which we will transform in stem cells and then differentiate in neurons. In particular the project is focused on a specific class of molecules, JNKs proteins which play an important role in regulate neuronal functions. Recently the partner Borsello has achieved experimental evidence on the therapeutic action of the D-JNKI1, a JNK-specific inhibitor peptide. She has preliminary data that after the treatment, synaptic alterations in neurons of models mice with Rett syndrome consistently ameliorate. It is a relevant finding considering the strong symptomatic overlap of Rett syndrome (RTT) with AS. Importantly the drug has already passed in clinical trials phase II and III for the cure of neurodegenerative diseases (ischemia)and apparently it is not toxic. The aim of this proposal is to investigate the involvement of JNK protein in the Angelman syndrome and to experiment the therapeutic effect of the D-JNKI1 peptide.
“Quantifying EEG abnormalities and identifying biomarkers in Angelman Syndrome”
Epilepsy is common both in individuals with Angelman syndrome (~90%), and neural signatures underlying epilepsy can be measured non-invasively using electroencephalography (EEG). AS patients have characteristic EEG patterns that have been described qualitatively by clinicians but not quantified rigorously using analytical methods. There is an unmet need to quantify EEG patterns in individuals with AS, and to gain insights into the circuit-basis for these abnormalities through parallel studies in AS model mice. We hypothesize that parallel studies of human and mouse EEG in Angelman syndrome using quantitative methods will dually provide clinical biomarkers and mechanistic insight. In collaboration with the two dedicated Angelman syndrome clinics in the United States, we aim to facilitate AS clinical trials by providing objective, unbiased biomarkers.
Geeske M. van Woerden – In vivocharacterization of E6AP interacting proteins
Erasmus University Rotterdam
Ben Distel – Elucidating the molecular mechanisms underlying E6AP function in the brain
Department of Neuroscience – ERASMUS MC
Scientific publications matter for ASA because they document the outcomes of the research we fund and that knowledge publicly available to the global scientific community.
In basic research – this is what ASA focusses funding on – this shared knowledge is what allows other scientists to build on discoveries and move the field forward.
| # | Title publication | Name of publication | Researcher funded by ASA | Year of publication | Link to publication |
|---|---|---|---|---|---|
| 1 | Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis | Journal of Neurodevelopmental Disorders | Ben Philpot | 2017 | Article |
| 2 | A versatile plasmid system for reconstitution and analysis of mammalian ubiquitination cascades in yeast | Microbial Cell | Ben Distel | 2018 | Article |
| 3 | Loss of nuclear UBE3A causes electrophysiological and behavioral deficits in mice and is associated with Angelman syndrome | Nature Neuroscience | Geeske van Woerden, Ype Elgersma & Ben Distel | 2019 | Article |
| 4 | JNK signaling activation in the Ube3a maternal deficient mouse model: its specific inhibition prevents post-synaptic protein-enriched fraction alterations and cognitive deficits in Angelman syndrome model | Neurobiology of Disease | Tiziana Borsello | 2020 | Article |
| 5 | Antisense oligonucleotide treatment rescues UBE3A expression and multiple phenotypes of an Angelman syndrome mouse model | JCI insight | Ype Elgersma | 2021 | Article |
| 6 | Loss of nuclear UBE3A activity is the predominant cause of Angelman syndrome in individuals carrying UBE3A missense mutations | Human Molecular Genetics | Ype Elgersma & Ben Distel | 2021 | Article |
| 7 | Mono-ubiquitination of Rabphilin 3A by UBE3A serves a non-degradative function | nature - Scientific reports | Ype Elgersma & Ben Distel | 2021 | Article |
| 8 | Crosslinked Chitosan Nanoparticles with Muco-Adhesive Potential for Intranasal Delivery Applications. | Int. J. Mol. Sci. | Laura Baroncelli & Ilaria Tonazzini | 2023 | Article |
| 9 | A stem cell-based toolkit to model Angelman syndrome caused by paternal uniparental disomy of chromosome 15 | Human Cell | Evguenia P. Bekman & Simão T. da Rocha | 2025 | Article |
| 10 | Generation of two pairs of induced pluripotent stem cells from Angelman syndrome patients with class I 15q11.2-q13.1 deletions and their unaffected familial controls | Stem Cell Research | Evguenia P. Bekman & Simão T. da Rocha | 2025 | Article |
| 11 | Dysfunction of the Autophagy System and MDM2–p53 Axis Leads to the Accumulation of Amyloidogenic Proteins in Angelman Syndrome Models | Int. J. Mol. Sci. | Laura Baroncelli & Ilaria Tonazzini | 2025 | Article |
| 12 | Crossing the finish line towards a disease-modifying treatment for Angelman syndrome | J Neurodev Disord. | Matthew C. Judson, Luis Pereira de Almeida, Rebecca D. Burdine, Stormy J. Chamberlain, Benjamin E. Deverman, Ben Distel, Michael D. Ehlers, Elizabeth Jalazo, Steven A. Kushner, Mark Nespeca, Stephan J. Sanders, Martin Scheffner, Jason J. Yi, Mark J. Zylka, Ype Elgersma, Benjamin D. Philpot | 2026 | Article |
The SAB plays a critical role in guiding ASA’s research priorities, ensuring that funded projects are scientifically rigorous and aligned with the organization’s mission. The Angelman Syndrome Alliance’s (ASA) Scientific Advisory Board (SAB) comprises leading experts in genetics, neurology, and related fields.
The main role of the SAB is to oversee the review of grant applications, and to offer advice and guidance to the ASA Board and ASA members.
Hanoch Kaphzan obtained an MD degree from Tel Aviv University. Following a few years as a combat surgeon, he specialized in psychiatry and became a board-certified psychiatrist. In addition, he graduated from a three-year program at the psychotherapy school to become a psychotherapist. Later, he obtained a PhD in neuroscience from the University of Haifa and continued his studies in neuroscience as a postdoc at New York University in New York, USA. On his return to Israel, he received a faculty position at the University of Haifa where he heads his lab. His research activity is mainly focused on two topics: the underlying cellular and molecular mechanisms of neurodevelopmental disorders with a special focus on Angelman syndrome, and the underlying cellular and molecular mechanisms of transcranial electrical neurostimulation. (Lab website)
Olga Peñagarikano is a Research Professor at the University of the Basque Country (UBC), Spain. She received her PhD in Human Genetics from UBC (2004) and completed a two-stage post-doctoral training at Emory University (Atlanta, USA) and at the University of California (Los Angeles, USA) working on the molecular basis and pathophysiology of neurodevelopmental disorders such as Fragile X and Autism (2004-2015). Her work received several awards including a “Top 10 Autism Research Achievements” (2011) from Autism Speaks and a NARSAD Young Investigator award (2015). Since 2015 she leads her own Research Group at UBC with focus on translational research of autism spectrum disorder and related disorders (www.penagarikanolab.org)
Jill Clayton-Smith graduated from the Victoria University of Manchester Medical School in 1982. After specialising in paediatrics, she entered Clinical Genetics in 1986 and undertook an MD at the Institute of Child Health London in 1989-1991. She became a Fellow of the Royal College of Physicians in 1999 and an honrary Professor of Medical Genetics in 2006.
Professor Clayton-Smith’s research interests include identifying the genetic basis and natural history of intellectual disability syndromes.
Her clinical specialist interests are in Angelman Syndrome, a neurodevelopmental disorder, and related conditions. She has been involved in this field for over 25 years.
(Centre for Genomic Medicine)
Luís Pereira de Almeida a prominent researcher in gene and molecular therapy for the Central Nervous System, has been a professor at the University of Coimbra since 2003. His work focuses on neurodegenerative diseases, especially Machado-Joseph disease. He leads research at CNC and CIBB and has published over 100 papers, cited over 13,000 times. He has mentored numerous postdoctoral fellows and PhD students, received numerous awards, and secured over €5 million in funding for his research projects.
The ASA board ensures that the goals set out are met.
From left to right:
Together we can fund more research.
Scientific Board reviews the proposal research projects.
We exchange regularilly best practices.
ASA is completely independent.
Any country that wants to contribute to the aims and goals of ASA is welcome. So in general every parent organisation that applies, can become a member. They have to commit to the following application process and rules.
Rights/duties of a Member:
Rights/duties of an associate:
ASA and ASF are partnering in the ANGELMAN Community Advisory Board (CAB) which provides expert advice to all stakeholders involved in the research, development and service provision of biomedical treatments for Angelman Syndrome.
The largest worldwide Angelman Community is formed by the cooperating parent organisations in the Angelman Syndrome Alliance (International) and Angelman Syndrome Foundation (USA). Both Foundations recognize that there is a compelling need for combined efforts to advance the work that is occurring in the Angelman Syndrome pharmaceutical and biomedical research space.
Who is on the Angelman CAB?
The ANGELMAN CAB is a group of patient advocates and expert patients/carers. They utilize their professional and personal knowledge and expertise to discuss and advise on the latest developments, challenges and issues related to Angelman Syndrome.
There is an internal board of voting members when votes are required, for example if we are asked to endorse pharmaceutical and/or biomedical research. The other CAB members are there to advise and participate in crucial conversations. Each member took part in hours of training with EURORDIS to prepare them for this role. There are a total of 20 members who represent all different corners of the world including Argentina, Austria, Belgium, Canada, Czech Republic, France, Germany, Russia, Hong Kong, Hungary, Israel, Italy, Japan, Netherlands, New Zealand, Portugal, Spain, Ukraine, the United Kingdom, and the United States of America.
The ANGELMAN CAB aims are as follows
Community Advisory Boards (CABs) are established, operated and maintained by patient advocates and expert patients. CABs are involved in scientific as well as policy-related issues in their disease area. They provide space to discuss the latest advances, challenges and issues related to medical treatments, medical devices, and procedures under development. This is an important initiative for the Angelman Syndrome community and for people affected by Angelman Syndrome globally.
What we can provide:
Angelman Syndrome is a rare genetic condition first identified in 1965 by British doctor, Harry Angelman, from whom it also gained its name. The syndrome – originally called ‘Happy Puppet Syndrome’ because of the characteristic happy demeanour and stiff jerky movements of the children – was renamed Angelman Syndrome in 1982. During the 1980’s advances in genetic medicine made it possible to diagnose increasing numbers of cases and also to start identifying the cause. In simple terms, it is a chromosome disorder that causes severe learning difficulties. It is now known that irregularities in Chromosome 15 are responsible for AS. However it is also known that there are several different irregularities that can occur in Chromosome 15, all of which result in a diagnosis of AS. Angelman Syndrome is not a disease, it is a neurological disorder that causes severe learning difficulties, and although those affected have a normal life expectancy, they will require looking after throughout their lives. Most AS children are diagnosed between the ages of 3 & 7 when the characteristic physical and behavioural features become evident.
The characteristics used for diagnostic criteria are listed below:
Consistent (100%)
Developmental delay, functionally severe
Speech impairment, no or minimal use of words, receptive and non-verbal communication skills higher than verbal ones
Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs
Behavioural uniqueness: any combination of frequent laughter/smiling; apparent happy demeanour; easily excitable personality, often with hand flapping movements; hypermotoric behaviour; short attention span
Frequent (more than 80%)
Delayed, disproportionate growth in head circumference, usually resulting in microcephaly (absolute or relative) by age 2
Seizures, onset usually by 3 years of age
Abnormal EEG, characteristic pattern with large amplitude slow-spike waves (usually 2-3/s) facilitated by eye closure
Associated (20-80%)
Flat occiput (bone at the back of the skull)
Occipital groove
Protruding tongue
Tongue thrusting; suck/swallowing disorders
Feeding problems during infancy
Prognathia (protruding lower jaw)
Wide mouth, wide-spaced teeth
Frequent drooling
Excessive chewing/mouthing behaviours
Strabismus
Hypopigmented skin, light hair and eye colour (compared to family), seen only in deletion cases
Hyperactive lower limb deep tendon reflexes
Uplifted, flexed arm position especially during ambulation
Increased sensitivity to heat
Sleep disturbance
Attraction to/fascination with water