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Celebrate Rare Disease Day
23 Feb

Celebrate Rare Disease Day

What is Rare Disease Day?

Approximately 30 million individuals in the United States are affected by a rare disorder or disease. On the last day of February every year, hundreds of patient organizations from more than 80 countries and regions worldwide conduct awareness-raising activities to celebrate Rare Disease Day.

The ASF is honored to celebrate Rare Disease Day with the AS community, Global Genes and all other organizations serving the rare disorder and disease community.
Here’s how you can get involved.

“Care About Rare”

Share your favorite photo of your loved one with AS on social media using these special frames to build awareness of AS and rare disorders, and encourage your friends and family members to do the same—it only takes a few steps! Here are some sample frames:

global jeans

Share Your Family’s Story with Global Genes Community

Share your family’s journey for a diagnosis with Global Genes and the rare disease community. Global Genes shares these family stories through its various channels, including newsletters, its website and social media, to raise awareness of rare diseases and disorders.

Check out the FitzGerald and the Bjorklund families’ stories below, both of whom have a loved one with AS.
Raise Awareness of AS in Your Community

Keep the momentum of International Angelman Day going!

  • Wear your AS- or ASF-branded clothing around town and have conversations with as many folks as possible—and direct them to Angelman.org!
  • Ask your employer, friends and neighbors to set up change jars at their offices, and collect funds for AS research.
  • Change light bulbs to blue—the traditional color for AS awareness—and tell people why!
  • Do a balloon release in honor or memory of our loved ones with AS.

Journey towards a diagnosis: The FitzGerald’s and the Bjorklund’s

The FitzGerald Family

The FitzGerald FamilyDrew was born in 2005 to Brian and Suzie FitzGerald, and he hit all of the usual developmental milestones during his first few months in this world. He was holding his head differently, so the FitzGerald’s began physical therapy, which progressed well and resolved the issue. However, at seven months old, Drew began missing milestones, and they started occupational therapy, still not thinking that anything major was amiss. A few months later, a neurologist tested him for Fragile X syndrome, but that came back negative. An additional few months later, an MRI revealed a minute issue but the doctors were not concerned. At just over a year old, the FitzGerald’s were noticing more developmental delays, and they were referred to a Developmental Pediatrician in Cleveland. This doctor was familiar with Angelman syndrome and after a two-hour visit, she told the FitzGerald’s that she wanted Drew tested for it. At this time, Suzie was pregnant with the family’s second son, Peter. Two weeks after Peter was born, the results came in: Drew was officially diagnosed with uniparental disomy Angelman syndrome, a rare type of Angelman syndrome.

The emotional upheaval experienced by the FitzGerald’s during this time—months of trying to get a diagnosis, then learning the diagnosis while welcoming a second child into the world—may sound familiar to some, but it’s completely foreign to many. Brian Fitzgerald recalls, “When I got the call about his diagnosis while I was at work, I immediately started looking up information online to learn about Angelman syndrome, as we had never heard of it before. I looked at the possibilities and what to expect, and I was devastated and torn-up inside. My son will never be able to do this, or do that. I had an hour-long drive home, and on my way home I realized something…these were things that I wanted for Drew, not things that Drew necessarily wanted. At that point, I realized it will be okay, and that we can and will do whatever we can to make sure Drew reaches his maximum potential, whatever that might be.” The FitzGerald’s also had Peter tested for Angelman syndrome, which came back negative. Though devastated at first, Drew had already been going through various therapies, so the family felt like they were ahead of the game by having already started therapies so young. And a couple months later, within a week of his second birthday, Drew took his first steps—something that some individuals with Angelman syndrome do not accomplish in their lifetime.

Over the years, the FitzGerald’s experienced difficulties getting Drew the right therapies and treatments that he needed, and to this day they are still searching the best practitioners to support Drew. However, Drew continues to succeed in his current therapies and achieve developmental milestones that some thought he would never reach, and his parents never lose faith, hope and encouragement. The FitzGerald’s also took their love for their son a step further: Brian had a group of buddies who play paddle tennis, and over time had built it into a community-wide championship called the Blarney Cup. To raise awareness and support for other individuals with Angelman syndrome, they turned the Blarney Cup into a fundraiser for the Angelman Syndrome Foundation. In 2014, the Blarney Cup raised and donated more than $30,000 to the Angelman Syndrome Foundation, and the 2015 Blarney Cup—taking place on March 6 and 7, 2015—is shaping up to break past records of attendance and funds raised. But the FitzGerald’s never forget the true inspiration behind all of their efforts: Drew, and his ever-present smile.

 

The Bjorklund Family

The Bjorklund FamilyAnika and Sophia Bjorklund, identical twins who are now 6-½ years old, were born premature and spent 25 days in the NICU because of feeding issues. Over time, they were monitored by pediatricians and despite parents’ Francesca and Eric’s concerns that their daughters were missing developmental milestones, the doctors indicated that they were simply “delayed.” Fast-forward 18 months and the girls were diagnosed with cerebral palsy. They were also diagnosed with autism, which remains a diagnosis for the Bjorklund twins. While living at West Point, and while Eric was deployed, Francesca met with a team of doctors there, who suggested they conduct genetic testing to “rule anything out.” The girls had already started a variety of therapies—including physical, speech and occupational—because of the cerebral palsy diagnosis, and they were progressing well physically but not well with fine motor and oral motor skills.

It was then that the diagnosis of deletion-positive Angelman syndrome came back, a couple days apart, for each of the girls. At first, Francesca experienced feelings of frustration and sadness after realizing that she and Eric may not have the “perfect children” they always envisioned. But then, sadness turned to determination and perseverance, as both parents focused on the many positive attributes of the girls—the girls are such happy individuals, and no disability or diagnosis was going to come in Francesca and Eric’s way in providing the twins with a life full of possibilities and experiences. Since the diagnosis rendered little changes to the current therapies the twins were undergoing, the Bjorklund’s focused on their ultimate goal: what should we be doing to ensure our girls reach their full potential?

The answer was simple, according to Francesca: our kids can do what other kids can do; it just takesmotivation, a lot of very, very hard work, and a plan to get there. Francesca surrounded herself with positive people, and connected with the Angelman Syndrome Foundation for resources and to find other AS families in her area, an experience that she says was invaluable during this difficult time of transition and learning. First, because they were twins—two toddlers to carry around rather than just one!—Francesca focused on walking. The girls, by nature, are very determined individuals, and at 2-½ years old, Sophia took her first steps out of her Kaye walker. Two days later, Anika joined her. “Without a hope, a dream, or a vision, you’ll never get there,” said Francesca. “You have to craft that vision, that path, because it is all about options and possibilities and choice. Don’t let anyone tell you that your kids can’t do something—they can, and with the right plan in place, they will.” And it is that mantra that continues to drive the Bjorklund family today, which was again recently tested by the twins beginning to learn to ride bikes at 6-years-old. “Pedal Perfect” became a dream and with the help of AMBUCS, adaptive bicycles were outfitted. As the girls have been learning to ride in the cold winter the glow on the girls’ faces is beyond enormous—it literally lights up the neighborhood, and fills the Bjorklunds with even more hope and promise for the future: the Bjorklund twins, with the right energy and support from their parents, are driven to excel at anything they put their minds to.

13 Feb

Hope for Thousands on International Angelman Day

ASF-Funded Research Illustrates Promise for Treatments for AS

The Angelman Syndrome Foundation (ASF) joins the international Angelman syndrome community in celebrating International Angelman Day on Sunday, Feb. 15 as ASF-funded research continues to make headway in identifying potential treatments for Angelman syndrome. Angelman syndrome is a severe, neurogenetic disorder related to and often misdiagnosed as autism and cerebral palsy that occurs during fetal development and lasts for a lifetime. While there is no definitive count, it is estimated that Angelman syndrome occurs in one in every 15,000 live births.

“We have much to celebrate during this year’s International Angelman Day,” said Eileen Braun, executive director of the ASF and mother to Kaitlin, who is diagnosed with Angelman syndrome. “Past and current ASF-funded research gives us hope that one day our loved ones with Angelman syndrome will have a better ability to overcome many of the challenges they currently face. Furthermore, successful Angelman syndrome research delivers hope to an even broader community of individuals because of Angelman syndrome’s genetic connection to several other disorders, including Prader-Willi syndrome and autism.”

Most recently, ASF-funded research conducted by Dr. Art Beaudet—a prominent Angelman syndrome researcher—at Baylor College of Medicine continues to move closer towards potential clinical trials, a tremendous beacon of hope and promise for the Angelman syndrome community. Research in ongoing but pre-clinical trials in mice have proven that symptoms of Angelman syndrome can be reversed, though more testing is needed to determine exactly how the cognitive deficits associated with Angelman syndrome are recovered.

Individuals with Angelman syndrome experience a variety of symptoms, including severe developmental delays, speech impairments, walking and balance disorders, and frequent laughter and excitability, though symptoms vary from individual to individual. More than 80 percent of individuals with Angelman syndrome experience seizures, which can be life threatening. While research such as Dr. Beaudet’s and others’ has shown potential to reverse symptoms of Angelman syndrome, past ASF-funded research has already proven successful in reducing symptoms or their severity, including Dr. Ron Thibert’s low-glycemic index treatment for seizures conducted at Massachusetts General Hospital and Dr. Jane Summers’ research proving improvements in neurodevelopmental outcomes from behavioral intervention.

ASF-funded research at the University of North Carolina-Chapel Hill, led by Dr. Ben Philpot and Dr. Mark Zylka, is also continuing to make headway in learning more about the Angelman syndrome gene, UBE3A, and how it interacts with an FDA-approved drug to potentially reverse symptoms. Their research also has implications for autism and chemotherapy treatments, as recently reported in the News & Observer in Raleigh, N.C. See additional promising ASF-funded research.

“Our goal is to better understand the genetic intricacies of Angelman syndrome so we can develop treatment strategies to help individuals with Angelman syndrome live a better life,” said Philpot. “ASF pilot funds have led to million dollar grants for Angelman syndrome research from the Simons Foundation and the National Institute of Health, and we continue to make headway because of the support of the ASF and the Angelman syndrome community.”

Later this year, the ASF will be awarding its 2015 ASF Funded Research Grants, providing more than $1 million to Angelman syndrome researchers to further our understanding of Angelman syndrome with the ultimate goal of finding a cure. In honor of International Angelman Day on Feb. 15, the ASF is asking for “$15 for the 15th” specifically in support of Angelman syndrome research.

30 Jan

Sensory-Friendly Films

AMC Hosts Sensory-Friendly Films in Partnership with Autism Society

AMC Theatres brings sensory-friendly films to families affected by autism and related disorders, such as Angelman syndrome, on a monthly basis to select communities. The Sensory-Friendly Films program provides a special opportunity for families to enjoy their favorite films in a safe and accepting environment. The auditoriums dedicated to the program have their lights up, the sound turned down, and audience members are invited to get up and dance, walk, shout or sing!

Films include the latest releases and other films, and are typically hosted once a month at nearly 100 theatres across the country. All showings are at 10:00am local time on Saturdays.

See the schedule of upcoming films and participating AMC theatres.

08 Dec

Health Issues in Adults with Angelman Syndrome

Research Investigates Health Issues in Adults with Angelman Syndrome

Dr. Ron Thibert, the well-known Angelman syndrome clinician and champion of the low-glycemic index dietary seizure treatment, and Dr. Anna Larson, both of Massachusetts General Hospital, published the findings from their clinical investigation into health issues that adults with AS experience.

The research team conducted standardized phone interviews with caregivers for 110 adolescents and adults with AS aged 16 to 50 years old. The impact of age, gender, and genotype on specific outcomes in neurology, orthopedics, internal medicine, and psychiatry were investigated, but did not address treatment. Further work should continue to refine the observable characteristics of older individuals with AS. Primary areas of clinical management identified in this research include seizures, sleep, aspiration risk, GERD, constipation, dental care, vision, obesity, scoliosis, bone density, mobility, communication, behavior, and anxiety.

The following is a summary of their findings.

Active Seizures

  • Present in 41% of individuals
  • Epilepsy severity may assume a bimodal age distribution: seizures are typically most severe in early childhood but may recur in adulthood

Sleep Dysfunction

  • Present in 72% of individuals
  • Late-adolescent and adult sleep patterns are improved when compared to the degree of sleep dysfunction present during infancy and childhood
  • However, prevalence of poor sleep in adults remains quite high

Significant Constipation

  • Present in 85% of individuals

Overweight / Obesity

  • Present in 32% of individuals, with obesity disproportionately affecting women

Scoliosis

  • Affects 50% of individuals with an average age of diagnosis at 12 years old
  • 24% of those diagnosed with scoliosis required surgery, an intervention disproportionately affecting men

Walking

  • 68% are able to walk independently

Speaking

  • 13% are able to speak 5 or more words

Self-Injurious Behavior

  • 52% of individuals exhibit self-injurious behavior

Click here to access the American Journal of Medical Genetics paper.

 

01 Dec

Possible Therapeutic for Angelman Syndrome

ASF-Funded Research Discovers Possible Therapeutic for Angelman Syndrome

Promising ASF-funded research continues to move closer toward possible clinical trials, as announced today in a paper in Nature by Dr. Art Beaudet and his research team at Baylor College of Medicine.

The ASF funded this research in its 2011 and 2013 research grant cycles, as part of its $8 million and growing investment in AS research with the ultimate goal of finding a cure for AS.

More research will be conducted but pre-clinical trials in AS mice have proven that the paternal copy of Ube3a can be activated and that AS symptoms can be recovered, though more testing is needed to determine exactly how the cognitive deficits associated with AS are recovered.

Dan Harvey, chairman of the ASF’s Scientific Advisory Committee, has interpreted the research for AS families and developed the following summary about the research.

Background
Neurotypical individuals have two versions of the Angelman syndrome gene (UBE3A), one from their mother (the maternal copy) and one from their father (the paternal copy) but only the one from the mother is expressed or “active.” In Angelman syndrome, the maternal copy is missing (deleted) or altered in some way to render it inactive. In 2008, Goal #1 of the ASF Research Roadmap was to aggressively explore activation of the silenced or “inactive” paternal copy of the AS gene (UBE3A) as a potential treatment for Angelman syndrome. The studies described in this article for Nature are the culmination of those efforts.

Summary
Recent studies by Philpot and colleagues demonstrated that Topotecan, a natural product derivative with various uses, unsilences the paternal copy of the AS gene in a non-specific manner. In this new article for Nature by Dr. Beaudet, Dr. Meng and their colleagues, it is demonstrated that a small DNA analog, known as an antisense oligonucleotide or ASO, can interact with the paternal copy of the AS gene and unsilence it in a highly specific manner.

Initial studies done with isolated neurons demonstrated that treatment with an ASO causes a long-lasting unsilencing of the paternal copy of the Ube3a gene.

Subsequent studies were done with AS mice. The ASO was directly injected into the brain of an AS mouse via a technique known as ICV (intracerebroventricular) injection. The ASO was well tolerated and partially unsilenced the paternal copy of the Ube3a gene. Additionally, it was highly specific for the AS gene, with no impact on other genes. Its activity was long lasting with unsilencing still observed sixteen weeks after treatment. When injected directly into a specific region of the brain know as the hippocampus, the part of the brain that manages cognition and learning, complete unsilencing of the paternal Ube3a was observed in the vicinity of the injection site.

Four weeks after treatment, AS mice treated with an ASO were subjected to behavioral testing and several of the behaviors typically observed in AS mice were reversed. In particular, memory impairment observed with AS mice was reversed after treatment. More extensive reversal of AS characteristics may require treatment at a younger age, a longer recovery time after treatment to allow greater rewiring of neural circuits, or a higher dosage of ASO.

In conclusion, the paper states: “Well tolerated delivery, broad tissue distribution, and long duration of action sets a framework for ASOs as a viable therapeutic strategy for diseases of the CNS (central nervous system), and builds enthusiasm toward further optimization and development of an ASO treatment for AS.”

View information about this study on Nature Journal of Science website. 

17 Nov

Research at UNC Making Progress

PNAS Paper shows ASF-funded Research at UNC Making Progress

The ASF continues to lead the charge in funding research that is making progress towards treatments and ultimately a cure for Angelman syndrome, having invested more than $8 million during the past decade in promising AS research.

A paper published today in the Proceedings of the National Academy of Sciences by Dr. Ben Philpot, Dr. Mark Zylka and Dr. Angela Mabb at the University of North Carolina at Chapel Hill uncovered additional findings about the Angelman syndrome gene, UBE3A.

Background

Neurotypical individuals have two copies of the Angelman syndrome gene (UBE3A), one copy inherited from their mother (the maternal copy) and one from their father (the paternal copy).  Only the maternal copy of UBE3A is “active” in neurons, thus mutation or deletion of this copy is sufficient to cause Angelman syndrome. The primary goal of the 2008 ASF Research Roadmap was to aggressively explore activation of the silenced or “inactive” paternal copy of UBE3A as a potential treatment for Angelman syndrome.

Summary

Recent studies by Dr. Ben Philpot, Dr. Mark Zylka, and Dr. Angela Mabb and their colleagues at the University of North Carolina at Chapel Hill demonstrated that Topotecan, a natural product derivative typically used to treat cancer, can unsilence the paternal copy of UBE3A. Topotecan thus represents a potential treatment for Angelman syndrome.  However, it is essential to understand the potential side effects and the impacts of using Topotecan on brain function before moving into clinical trials.  Accordingly, the studies described in this article from the Proceedings of the National Academy of Sciences continue the research group’s previous research in an effort to determine the consequences of using Topotecan or similar inhibitors in the brain.

The team took a step back from the mouse model and used an in vitro model, or neurons in a petri dish, because this provides a system to reliably and consistently deliver Topotecan to neurons.

This article illustrated that when neurons were treated with Topotecan, the goal of unsilencing the paternal copy of UBE3A was accomplished. However, during treatment, the neurons experienced a complete shutdown of activity—UBE3A was activated, but the specific cells that were treated stopped communicating with each other. However, normal neuronal activity was quickly restored once Topotecan was removed.  This result is exciting because it suggests that most treatment side effects are likely to be fully reversible.

A goal of the research is to find a treatment strategy that can provide long-term UBE3A unsilencing, as was observed with their previous research, such that the side effects of Topotecan can be completely recovered in the short-term, as was observed in the current study.

The next step to this research is to identify novel and more efficient delivery methods using Topotecan or other inhibitors like Topotecan in an AS animal model to unsilence UBE3A, to evaluate potential side effects of these treatments, and to see if Angelman syndrome symptoms in the mouse model can be reversed following drug treatment.
Click here to access the PNAS paper.

09 Jan

AS Research at Baylor University Makes Significant Progress

AS research at Baylor University Seeking Viable Treatment Makes Significant Progress

The Angelman Syndrome Foundation and the lab of Arthur Beaudet, M.D., at Baylor University are inspired and excited to announce that progress is being made in analyzing a possible avenue of treatment for Angelman syndrome.

The research, funded by the Angelman Syndrome Foundation in the organization’s 2011 and 2013 research grant cycles, seeks to find a possible treatment for Angelman syndrome by activating the paternal copy of Ube3a in a mouse model.

Ongoing research and this latest discovery, published in December in PLOS Genetics, have demonstrated the feasibility of activating paternal Ube3a in mice by terminating the transcription of its antisense RNA Ube3a-ATS genetically.  In doing this in the AS mouse model, the research team observed restoration of Ube3a expression, improvement of behavioral defects, and reversal of the impaired long-term potentiation.  The research team further studied the imprinting mechanisms of Ube3a and proposed a novel transcriptional collision model.  These results provide evidence for a key regulatory role of Ube3a-ATS in Angelman syndrome, opening up an exciting possibility of a gene-specific treatment for Angelman syndrome.

“We at Angelman Syndrome Foundation are optimistic about the future of this research, as our ultimate goal is finding viable treatments and a cure for our loved ones with Angelman syndrome,” said Eileen Braun, executive director of the Angelman Syndrome Foundation.  “Our Scientific Advisory Committee goes through a rigorous process in evaluating research projects for potential grants, and we are all thrilled with the results coming from the Beaudet lab.  We are incredibly appreciative of the Baylor team’s dedication to creating a better future for individuals with Angelman syndrome.”

For more information about the research or the Angelman Syndrome Foundation’s 2013 research grants, please click here.

28 Aug

Research on Topoisomerase Inhibitors

University of North Carolina-Chapel Hill Research Overview and Frequently Asked Questions

The Angelman Syndrome Foundation previously supported breakthrough research showing that topoisomerase inhibitors—specifically, topotecan, an FDA-approved drug used in cancer treatments—activates the paternal allele of Ube3a, identifying a possible treatment for Angelman syndrome. The continuation of that research at the University of North Carolina-Chapel Hill has extended the possibility of using topoisomerase inhibitors to treat individuals with Angelman syndrome, and has also identified possible side effects of these drugs on the developing brain. This research is the first to show that topoisomerase inhibitors unsilence Ube3a both in a mouse model and, because of collaborative work with Dr. Stormy Chamberlain at the University of Connecticut, in stem cell-derived neurons from an individual with Angelman syndrome (deletion positive). This study thus demonstrates how Ube3a can be reactivated in patient-derived neurons. The researchers also found that in the process of activating the paternal copy of Ube3a, topotecan reduced the levels of other genes that are linked to autism, which has the potential to result in characteristics of autism in individuals. This research suggests there may be trade-offs in using these drugs to unsilence Ube3a in individuals with Angelman syndrome, and could provide insights into why mutations in topoisomerases are linked to autism. This research also highlights the continued importance of defining a critical treatment window for topoisomerase inhibitors, to determine when these drugs have their best chance of being effective while minimizing side effects on the developing brain. Most importantly, this study highlights the importance of supporting rigorous preclinical research on topoisomerase inhibitors, or any other drugs, prior to advancing into clinical trials for individuals with Angelman syndrome. Access the abstract published in Nature,

Frequently Asked Questions

1. What is Angelman syndrome’s correlation to autism and how are they linked already?

  • While some doctors, scientists and researchers do and some do not consider Angelman syndrome to be an Autism Spectrum Disorder (ASD), all can agree that there is, to a certain extent, a connection between the two. What is known so far is that:
    • Not enough or improper function of the Ube3a gene = Angelman syndrome
    • Too much functionality of the Ube3a gene = ASD
  • A few developmental and behavioral characteristics do overlap between Angelman syndrome and ASD, yet the main behavioral differentiator is that individuals with Angelman syndrome do not feel the extreme aversion to social situations as do individuals with ASD.
  • Individuals with Angelman syndrome are able to read facial expressions, body language and vocal intonations extremely well, and as a result, they enjoy and seek out social interaction.

2. How are topoisomerase inhibitors linked to autism?

  • Topoisomerase inhibitors activate the paternal copy of the Ube3a gene but in doing so, they also reduce the levels of other genes linked to autism. It is currently unknown if this could result in characteristics of autism in individuals. With proper timing, it may be possible to activate Ube3a while minimizing side effects associated with reducing the levels of genes linked to autism.
  • The effects on autism genes were only present for as long as the topoisomerase inhibitors were present; once the drug wore-off, gene expression returned to baseline levels. However, it is important to note that mutations in topoisomerases have surfaced in some individuals with autism, suggesting that an alteration in the activity of these enzymes increases the risk for autism. This further suggests it may be possible to time drug administration to minimize side effects during critical periods of brain development.

3. Why is the Angelman Syndrome Foundation funding this research?

  • The Angelman Syndrome Foundation was the first to fund this pioneering research at UNC in 2009. This research identified 16 different topoisomerase inhibitors that could unsilence paternal Ube3a, making these the first potential treatments for Angelman syndrome. This was also the first research to show that the paternal Ube3a could be unsilenced, paving the way for all future efforts to reactivate this gene that is linked to Angelman syndrome.
  • As the research study continued to progress and illustrate promising results, UNC applied for funding to continue the research, and the Angelman Syndrome Foundation awarded a research grant for its continuation (in addition to other organizations providing funding as well).
  • The Angelman Syndrome Foundation will continue to fund this research as part of its 2013 research grant cycle to determine the treatment window and autism-related side affects of topoisomerase inhibitors as a potential treatment for Angelman syndrome.

4. How could this research impact my individual who has Angelman syndrome, or for my individual who has a dual diagnosis of Angelman syndrome and autism?

  • Currently, topoisomerase inhibitors, while having shown potential, are not currently used to treat individuals with Angelman syndrome. As with any new or repurposed drug, extensive preclinical and clinical work must be done to establish safety and efficacy.
  • This research is still in pre-clinical phase and more work is being done before it has the potential to move to a clinical trial.

5. What are the next steps?

  • The research team is currently identifying the potential critical window for treatment, and what factors are involved within that critical window: identifying when topoisomerase inhibitors have their best chance of being effective, and if and when topoisomerase inhibition increases susceptibility to autism.

6. If we don’t get a “cure” from this research, then what are we getting from this research?

  • This research provides the first evidence that a drug can be used to turn on the paternal copy of Ube3a. Restoring Ube3a levels represents a critical path towards any cure or treatment for Angelman syndrome. Prior to this research, most would have thought it impossible to reactivate a silenced gene. Angelman Syndrome Foundation-funded research has shown that the impossible can be done, by supporting rigorous science and scientists who are truly committed to helping individuals with Angelman syndrome.
  • This research has spurred many other investigators to identify additional drugs that reactivate Ube3a, including promising work with antisense oligonucleotides that specifically target the antisense transcript that topoisomerase inhibitors regulate. As with topoisomerase inhibitors, there will likely be the need for numerous studies that define the optimal treatment window to ensure the drugs reach their intended target in the brain.
  • This research is beneficial to the overall Angelman syndrome community because it has identified possible side effects from using topoisomerase as a potential treatment for Angelman syndrome before this moves to clinical trial.

7. How much did the Angelman Syndrome Foundation fund for this endeavor, and how much will the organization continue to fund?

  • The Angelman Syndrome Foundation originally funded $199,972 for the initial research project in 2009.
  • UNC applied for continued funding for this project in 2011 and received $510,000 collectively in funding from the ASF’s 2011 Research Grants. These funds were awarded in two two-year grants of $200,000 each to Dr. Mark Zylka and Dr. Ben Philpot, with an additional $110,000 awarded to Dr. Ian King as part of the Angelman Syndrome Foundation’s Joseph E. Wagstaff Postdoctoral Fellowship.
  • UNC applied again in 2013 to continue this promising research, and the Angelman Syndrome Foundation continued to fund this research as part of its 2013 research grant cycle to determine the treatment window and the possible side affects of using topoisomerase inhibitors as a potential treatment for AS. These funds were awarded in two two-year grants of $200,000 each to Dr. Mark Zylka and Dr. Ben Philpot, with an additional $110,000 awarded to Dr. Angela Mabb as part of the Angelman Syndrome Foundation’s Joseph E. Wagstaff Postdoctoral Fellowship.
  • If UNC decides to apply for the ASF’s 2014 research grants for additional funds for this or other AS-related research, the ASF would evaluate that research proposal at that time.

This study is one of several ASF research initiatives that investigate potential treatments for AS. In addition to exploring topoisomerase inhibitors, the ASF is currently funding research that studies the ability of antisense to awaken the paternal Ube3a gene and the optimal time to administer treatment.

18 Jun

Angelman Syndrome Foundation Invests $1.25 Million in Research

Angelman Syndrome Foundation Invests $1.25 Million in Research

The Angelman Syndrome Foundation (ASF) announced today that because of the generosity of its supporters the organization has awarded $1.25 million to six research grants focused on finding treatments and defining the optimal window for treatment for individuals with Angelman syndrome, a neurodevelopmental disorder which can be similar to autism.  ASF leadership approved $250,000 more than the original $1 million call for research proposals earlier this year due to the nature of the research studies and their potential impact on all ongoing Angelman syndrome, autism and other developmental disorder-related research.

“Angelman syndrome research continues to edge closer and closer to potential life-changing treatments and opportunities for individuals with Angelman syndrome, and it is because of the tremendous support of our community that the ASF is able to invest in these important research endeavors that are quintessential to the success of all future AS preclinical and clinical trials,” said Tim McCarty, president of the ASF board of directors.  “The ASF’s Scientific Advisory Committee and leadership team have evaluated these research projects thoroughly and are confident in the direction they advance Angelman syndrome research, while also furthering the advancement of related neurodevelopmental disorders including autism.  Families, friends, loved ones and others close to individuals with Angelman syndrome who have supported the ASF during our National Walk and other times of the year have made this research investment possible.”

In evaluating this year’s research proposals, the ASF Board of Directors and Scientific Advisory Committee focused on proposals that sought to discover new therapeutics for Angelman syndrome or to better understand the scientific complexities of Angelman syndrome.  This year’s Angelman syndrome research grants are significant as they seek to further define the optimal age at which to administer treatment, or the treatment window, and they further test an already FDA-approved drug as being a viable overall treatment for Angelman syndrome.

The breadth and depth of ongoing Angelman syndrome research, which is leading closer towards a cure, makes available the opportunity for this year’s funded research projects to also further the understanding of varying UBE3A gene mutations and deletions, the causative gene in Angelman syndrome.  Additionally, this year’s funded research seeks to further understand learning and memory deficits in individuals with Angelman syndrome and how they impact individuals genetically and behaviorally.

“Not all individuals with Angelman syndrome have the same genetic blueprint that causes the symptoms of Angelman syndrome, which is also why our leadership team believed that each of these research projects is important,” said Eileen Braun, executive director of the ASF.  “We want to more fully understand and be able to treat what is causing the symptoms of Angelman syndrome in each individual and help improve his or her quality of life.  The strides that research in recent years has made sets an excellent stage to build upon and we are optimistic about the direction of this year’s funded research and the further building blocks it will create.”

Research grants were awarded to:

  • Ben Philpot, Ph.D. of University of North Carolina–Chapel Hill, and Ype Elgersma, Ph.D. of Erasmus Medical Center, Rotterdam, Netherlands
  • Arthur Beaudet, M.D. and Linyan Meng, Ph.D. of Baylor College of Medicine, Houston, Texas
  • John Lisman, Ph.D. of Brandeis University, Boston, Mass.
  • Jason Shepherd, Ph.D. of University of Utah, Salt Lake City, UT
  • Craig Erickson, M.D., of Cincinnati Children’s Hospital Medical Center
  • Mark Zylka, Ph.D. of University of North Carolina–Chapel Hill

ABOUT THE ANGELMAN SYNDROME FOUNDATION

The Angelman Syndrome Foundation’s mission is to advance the awareness and treatment of Angelman syndrome through education and information, research, and support for individuals with Angelman syndrome, their families and other concerned parties.  As the largest non-governmental funder of Angelman syndrome research, the ASF sponsors Angelman syndrome research through grants to researchers pursuing promising avenues of discovery.  Since 1996, the ASF has funded 72 research grants totaling more than $5.8 million.  The ASF has awarded a majority of these funds ($5.5 million) beginning in 2005.