Angelman Syndrome Research

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Assert is fully committed to supporting research projects into Angelman Syndrome and related areas. To date we have supported research into a variety of areas, including:

  • Behaviour in AS individuals.
  • Stress in parents of AS individuals and the effects of this on the immune system.
  • Health and well-being in AS individuals.
  • ASSERT’s own research into AS, characteristics and incident rates.

We are always interested in hearing about new research projects relating to Angelman Syndrome and its associated issues, so please feel free to contact us if you feel your research may be of interest to us.

We will in the near future be posting more details of the research we have been involved with on this web site and we trust that you will find this information both informative and helpful.

Please note

All research notes are provided for information purposes only and Assert do not necessarily endorse any particular treatment. We have attempted to provide a brief and simplistic overview of current research and we therefore advise any readers who require more detailed information to conduct further investigation via the links provided on our Downloads page, by searching the internet for recent articles or by contacting the organisations directly involved.

We would also like to emphasise that while all of the current ongoing research is exciting and is a source of hope in the treatment and management of AS, it should be understood that all research projects can take considerable time from experiments in animal models to treatment being available to humans.

There is also great concern in the research community that now specific medications are being discussed as part of the research and in some cases actually trialled, that some parents in their desperation to alleviate the issues endured by their AS children may be tempted to self prescribe these medications to their children. ASSERT would strongly advise against this as it needs to be recognised that any clinical trials that are currently ongoing are carried out under strict conditions, monitoring and guidance of the research organisations and their associated medical professionals. At present it is not known what side effects the use of these medications may have with individuals with AS.

Dick Barton Research Fund

Assert have set aside a small amount of money to be allocated towards funding small research projects which the trustees feel will have direct benefit to families and carers of AS individuals. If you would like to apply for funding for your research, please send details of your research project to the chair of the trustees.

Dick Barton was a much loved grandfather and long serving, committed trustee for Assert who sadly passed away in 2007.

What is UBE3A?

The most common genetic defect leading to Angelman syndrome is a maternal deletion of DNA from chromosome 15, causing an absence of expression of the UBE3A gene in the paternally imprinted brain regions.

Everyone has two copies of the UBE3A gene, one from their mother and one from their father. But due to a biological quirk, we only use the gene we inherit from our mothers. The majority of individuals with Angelman Syndrome either have deletions that remove the mother’s copy of UBE3A, or have mutations that prevent the mother’s supplied UBE3A gene from being functional. But each of these individuals has another copy – the paternal copy – of the UBE3A gene that isn’t being used.

One strategy of current research (the focus of the Huang-Philpot-Zylka team, see below) is to resupply UBE3A itself to neurons that need it. Thus, the aim would be to find a drug or other method to ‘turn on’ the normally silent UBE3A gene inherited from the father. Researchers have found that the father’s UBE3A gene can be turned on to small degrees in different experiments. Thus under the right conditions, neurons can turn this gene on. There is now a need to find the right drug or treatment to do this to a larger sustainable degree.

A second strategy (the focus of the Edwin Weeber research, see below) is to find a way to restore neuronal function by correcting the issues caused by the lack of UBE3A. For example, in the mouse model for Angelman Syndrome, the learning and motor planning issues caused by loss of UBE3A can be compensated for by including another gene product in a form that is more active than usual. Thus if drugs or strategies can be found to enhance activity in neurons, this might also benefit individuals with Angelman Syndrome.

  • You will see UBE3A written in three different ways: Ube3a, UBE3A, UBE3A — What’s the difference? Different text formats are used to distinguish between genes and the proteins made from those genes.
  • In mouse, rat or chicken — the gene is referred to as Ube3a while the protein is Ube3Aa.
  • In humans and non-human primates — the gene is referred to as UBE3A while the protein is UBE3A.
  • In fruit flies — the gene is referred to as Dube3a and the protein is Dube3a.

For more information go to:

Topoisomerase inhibitors

During 2011 a team at the University of North Carolina School of Medicine (Dr. Hsien-Sung Huang, Benjamin Philpot and Mark Zylka) concentrated their research on finding a drug to re-activate the (dormant) paternal copy of the UBE3A gene, in the hope that it might restore some of the functions previously lost in individuals with AS.

Dr. Hsien-Sung Huang and colleagues tested over 2000 chemical compounds and found Topoisomerase 1 inhibitors to have an effect. Topoimerase inhibitors interfere with DNA replication, and have previously used to treat certain forms of cancer. The authors demonstrated that using Topoimerase 1 inhibitors, the re-activation of the paternal copy of the ube3a gene was possible in a mouse model.

It is hoped that this type of approach may lead to improvements in the condition of those with Angelman syndrome in future. What they have not done is reverse the symptoms of AS in a mouse model. This is the next step in their research.

Although some Topoisomerase inhibitors have been used for treating patients with cancer, they are not yet close to being used to treat Angelman syndrome. Mice can tolerate higher doses of the compounds than humans, and researchers don’t yet know how much would be needed for effective treatment.

Although the infrastructure for clinical trials of drugs for treating AS is already in place, a regulatory process for investigating new drugs would take several months. Huang and co-workers hope for clinical trials before too long.

“The really pressing concern is that people will start using off label,” explains Dr. Benjamin Philpot of the Huang team (in the U.S. Topotecan – a brand name for Topoisomerase inhibitors – is licenced for use by injection into the cerebrospinal fluid of adults with neoplastic meningitis, so in that country at least a physician could theoretically and legally be injected into the cerebrospinal fluid of a patient with AS). “Not only is it a risk to the individual, it could jeopardize future clinical trials.”

For more information go to: the UNC School of Medicine website.

Minocycline Trials

read full article …

At the Neurobiology of Learning and Memory Laboratory (NLML) in Tampa, Florida, a research team led by Edwin Weeber Ph.D. have recently claimed unexpected results while investigating Alzheimer’s Disease.

The aim of the NLML’s research is to find a way to restore UBE3A function to neurons in order to address the learning and motor planning issues caused by lack of UBE3A. This is in contrast to research attempting to re-activate the (dormant) paternal copy of the UBE3A gene (e.g. the topoisomerase inhibitor research described above).

According to Edwin Weeber:

“…this proposal does not focus, necessarily, on understanding mechanisms of AS but rather treating AS.”

The NLML team have indicated that their initial investigations have suggested that the brain and the neurons form correctly in an individual with AS, indicating that the neurons could function normally if UBE3A function could be restored. Their research suggests that the cognitive disruption observed in Angelman syndrome may result from disruption in CaMKII signaling. Importantly, αCaMKII is not produced until after birth, suggesting that postnatal therapeutic intervention may be possible.

The team is exploring several approaches to rescue the learning and memory deficits in AS mouse models. They state that the issues caused by loss of UBE3A could be compensated for by finding drugs or strategies to enhance CaMKII activity in neurons. Thus the NLML proposal is that if drugs or strategies can be found to enhance activity in neurons, this might also benefit individuals with Angelman syndrome. What’s more, if they concentrate their research on drugs that were already FDA-approved the process of bringing an effective treatment to market could be significantly quicker.

To this end the team identified Minocycline – a tetracycline-class antibiotic – as having the qualities they needed. This drug is primarily used to treat acne and other skin infections such as MRSA, as well as Lyme disease. The NLML team claim that Minocycline’s superior ability to cross the blood–brain barrier is the main reason for its effectiveness in treating their AS mouse model.

The next stage of research is to conduct human trials on AS individuals to establish the treatment’s effectiveness and the correct dosage. These trials started in May 2012, with the results due to be published in February 2013.

For more information go to:

Looking After a Child with an Intellectual Disability?

Parents, it’s time for your voices to be heard!
Article from Prof. Chris Oliver’s Team – University of Birmingham

Researchers at the University of Birmingham are starting two new research projects with families that have taken part in previous research studies.  It is hoped these projects will capture the lived experiences of these families.

When you think of a researcher what image comes to mind? Is it the stalked neck academic crunching numbers or figures, or is it the Professor boffin pouring over his dusty volumes of long lost research? How close do researchers come to capturing people’s everyday experiences of caring for children with intellectual disabilities? At the Cerebra Centre for Neurodevelopmental disorders (University of Birmingham) we have always been concerned about the views of parents of children with intellectual disabilities when forming our research questions. Hopefully, if you have taken part in these projects you have found them useful.  Despite this, there still seems to be a gap between those initial rich and complex conversations with parents that inspire our research and the facts and figures that get published in research journals – somewhere the human element gets a little lost. To some degree this is to be expected but ultimately we need to focus on what actually inspires policy change.  What makes services stand up and listen? Facts go a long way but can they ever match up to people’s stories about their experiences – stories about their children’s needs, parents’ perceptions of these needs and the services they may go on to access? We feel that these stories are powerful and that they can make a real difference when appealing to services, professionals and other researchers to step back and then make changes.

Children with intellectual disabilities have complex needs and a vast proportion of families caring for these children will experience difficulties for which they need support. Researchers now know quite a lot about the needs of children with intellectual disabilities, however, very little is currently known about how caring for a child with an intellectual disability affects parents and carers and about the quality of support they are receiving from services. It is time to close that gap between parents’ lived experiences and published research. We are beginning two new research projects with families who have already taken part in our research studies; therefore, we will be joining two powerful forces: your voices and our facts and figures. This way we can make an even bigger difference to children with intellectual disabilities and their families. If you have previously taken part in our studies we need your help so please keep an eye out for our questionnaire and interviews looking at children’s characteristics and needs, challenging behaviour, your thoughts and feelings and service provision. Letters or emails inviting you to take part in this research will be sent to you from September 2012. It is the time to have your say!

If you have any further questions or would like to request further information about this new area of research please do not hesitate to get in touch.

Email: Dr Jane Waite

Telephone: 01214147206