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.
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:
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.
Keep the momentum of International Angelman Day going!
Drew 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.
Anika 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.
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.
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.
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.
Overweight / Obesity
The Weisenfeld family spoke with CNN about their journey with Johanna, their 10-year-old daughter diagnosed with AS. A truly inspiring story to which almost all families can relate!
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.
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.
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.”
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.
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.
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.
Furthering its direct support of individuals with Angelman syndrome and their families, the Angelman Syndrome Foundation has committed $1.5 million to establish 17 comprehensive Angelman Syndrome Clinics across the country during the next few years. The ASF has strategically identified locations that are within a 4-hour driving distance for more than 85% of the AS population in the U.S.—meaning a majority of families (>85%) in the U.S. will not have to travel more than four hours to access their nearest clinic, which is a primary goal of the ASF’s in making the clinics as accessible as possible. Each clinic will receive a three-year funding commitment of $50,000 the first year, $30,000 the second year, and $10,000 the third year, to establish the clinics and support them until they are self-sustaining.
Currently, there are two Angelman Syndrome Clinics established in Chapel Hill, NC and Boston, MA. The ASF is in the final stages to open the next clinic in Rochester, MN and has requested proposals to establish the next clinics in San Diego and Houston, with Chicago to follow. In alphabetical order, future target cities include Atlanta, Cleveland, Dallas, Denver, Jacksonville, New York, Philadelphia, Salt Lake City, San Francisco, Seattle and St. Louis.
The purpose of the ASF’s Angelman Syndrome Clinics is to:
Every year, the Olsen Family—Keith, Denise and their children—hosts a Tractor Cruise fundraiser in support of the Angelman syndrome community. Held on Labor Day, this year’s cruise featured nearly 40 tractors that proceeded on a 40-mile trip on Brown County, Kansas roads. With beautiful weather for everyone to enjoy during the whole day, the group took a lunch break at the local Agricultural Museum, where the Brown County Historical Society helped serve a delicious meal for the cruisers—it was so good, there were no leftovers!
This is the ninth year that the Olsen’s have hosted the Tractor Cruise, and collectively have raised more than $25,000 in support of the AS community over the years! The Olsen’s are looking forward to the 10th anniversary Tractor Cruise next year during Labor Day weekend, which will also kick-off at Everest Middle School in Everest, Kansas.
Many thanks to the Olsen’s and their friends, family and supporters for their incredible support of our loved ones with AS!
Click here for more photos of the 2014 Tractor Cruise—it was a fun time had by all!