LADDER Database
25 Nov

LADDER logo

A new network platform, Linking Angelman and Dup15q Data for Expanded Research (LADDER), will offer caregivers access to information about a larger population of patients living with Angelman or Dup15 syndromes to better inform their decisions regarding treatments and interventions.

RTI International (RTI), a nonprofit research institute, together with Angelman Syndrome and Dup15q Patient Advocacy Groups and the 15q Clinical Research Network will develop and host the clinic network database to be shared across multiple national and international sites. This collaborative effort is funded by the Angelman Syndrome Foundation (ASF) and the Dup15q Alliance.

“The database will establish a global network of patient-powered data that will be used to improve care for people living with Angelman or Dup15q syndrome,” said Anne Wheeler, PhD project lead and RTI researcher at the Center for Newborn Screening, Ethics, and Disability Studies. “Furthermore, the heightened level of data analysis and discovery will increase our understanding of the disorder and help researchers target therapies and advance clinical trials more quickly and efficiently.”

Angelman and Dup15q syndromes are rare neuro-genetic disorders that result from changes on chromosome 15. These changes are estimated to occur in one in 15,000 live births. Characteristics or symptoms of Angelman syndrome and Dup15q Syndromes include developmental delay, lack of speech, seizures, and walking and balance disorders. Dup15q syndrome is highly additionally associated with autism and significant intellectual disabilities. Because of their genetic relationship to autism and other disorders, many researchers believe that curing Angelman or Dup15q syndromes will lead to significant findings for similar disorders.

“The combination of data collection methods and cross disorder investigation is key to driving discovery in rare disorders like Angelman and Dup15q Syndromes,” says Vanessa Vogel-Farley, Executive Director of the Dup15q Alliance. “We are proud to support this first-of-its-kind project in 15q related disorders.”

RTI will support the development of the database by:

  • Finalizing standardized forms for clinicians and parents;
  • Developing a website and portals for data entry;
  • Managing data from various clinic sites; and
  • Working with external partners, like the Angelman Syndrome Natural History Study and the Global Angelman Registry, to link other existing datasets to the prospective clinical data.

In addition to developing and hosting the database, RTI will assist the ASF and Dup15q alliance with data analysis and oversight, including establishing protocols and parameters for data usage and publication.

“We are excited to partner with RTI and DUP15q Alliance to provide a robust database that will be used to enhance research, care and aggressively move clinical trials forward,” says Amanda Moore CEO of ASF. “The ASF is honored to provide funding for such an essential database to support our mission of working towards a therapeutic cure.”

About RTI International
RTI International is an independent, nonprofit research institute dedicated to improving the human condition. Clients rely on us to answer questions that demand an objective and multidisciplinary approach — one that integrates expertise across the social and laboratory sciences, engineering and international development. We believe in the promise of science, and we are inspired every day to deliver on that promise for the good of people, communities and businesses around the world. For more information, visit www.rti.org.

Announcing the 15q Clinical Research Network
18 Nov

Angelman Syndrome Foundation and Dup15q Alliance Announce Development of the International Clinical Research Network in efforts to help those living with 15q syndromes. 

Thousands of families affected by Angelman syndrome (AS) and dup15q syndrome will soon have greater access to comprehensive clinical care through the development of The 15q Clinical Research Network. The Angelman Syndrome Foundation (ASF) and the Dup15q Alliance are proud to announce that through this collaborative effort the 15q Clinical Research Network would expand to 20 operating clinics to serve patients with Angelman syndrome or dup15q syndrome.

For more than a decade the ASF and Dup15q Alliance have been supporting multidisciplinary clinics to ensure up-to-date evidence-based clinical care for individuals with Angelman and Dup15q syndromes. What began as a few clinics has grown to almost 20 sites in the U.S. with four international sites between the two organizations. These clinics are working to standardize care for those with these disorders, a critical step forward as we approach clinical trials. Additionally, they serve as a platform for robust clinical research including collection of integral natural history data.

click to enlarge

Angelman and dup15q syndromes are two rare conditions that occur due to a problem with the same region of the 15th chromosome. Because of that, they share symptoms (developmental delays, GI problems, seizures) that often require specialized care. Due to the rareness of the syndromes, local general practitioners and even specialized doctors often do not have a thorough knowledge of the complications and treatments. To get the care they need some families have traveled far to receive care for their loved ones at the clinics that have dotted the U.S. map. 

Both foundations realized that there were far too many families who were not able to travel to receive specific care, so they embarked on a mission to dramatically expand the clinical reach of the networks and provide truly comprehensive care across the country by combining forces. 

ASF CEO, Amanda Moore, says, “We believe that partnering with the Dup15q Alliance will allow us to increase our reach to the AS community and provide the best care for our families. Comprehensive and specific care is critical for AS families throughout the stages of their journey — by partnering with Dup15q Alliance we are able to reach thousands of more families with care and support by bringing AS Clinics to their geographical location.”

The joint expansion of the clinical network will also expand the amount of clinical trial sites in the future, increase research and publications, and add important clinical data that can impact the therapeutic treatments around both disorders. 

Vanessa Vogel-Farley, Executive Director of Dup15q Alliance states, “One of the biggest challenges those who have 15q related disorders face is finding clinical support that is educated about their needs and that are effective activated partners in the complex medical care of their loved one. The collaboration between the Angelman and dup15q syndrome communities in the establishment of the 15q Clinical Research Network helps to alleviate that burden, by expanding the number of locations where expert providers are available, and  establish a system for transferring care of the patients back to their local providers through education and seamless communication with providers.”

This is the not the first time that ASF and Dup15q Alliance have worked together.  Because of the common issues with the 15th chromosome, the past several years ASF and Dup15q Alliance have co-hosted a research symposium every two years.  Many researchers that study Angelman syndrome also study dup15q syndrome and the research symposium brings them together to share ideas and collaborate, advancing research and clinical trials. 

Angelman syndrome is a rare genetic disorder caused by the loss of function of a specific gene (15q chromosome) during fetal development, resulting in severe neurological impairment present at birth and lasting for a lifetime. Symptoms vary and include severe developmental delays, speech impairments, seizures, walking and balance disorders, and frequent laughter and excitability. While there is no definitive count, it is estimated that Angelman syndrome occurs in one in every 15,000 live births.

Dup15q syndrome is a clinically identifiable syndrome that results from the duplication (or multiplication) of the same portion of the 15q chromosome that is deleted in Angelman Syndrome.  Also known as chromosome 15q11.2-q13.1 duplication syndrome, this is a neurodevelopmental disorder that confers a strong risk for autism spectrum disorder, epilepsy, and intellectual disability, etc. It is estimated to occur in one out of every 8,000-10,000 live births.

Zylka Lab at UNC awarded $6.1 million from NIH
18 Sep

This is what ASF Funded Research can do! 

A  UNC Healthcare announced on September 17, 2019:

The National Institutes of Health have awarded two separate grants totaling $6.1 million to Mark Zylka, PhD, director of the UNC Neuroscience Center. One of the grants was co-awarded to Ben Philpot, PhD, associate director of the center at the UNC School of Medicine.

One of these projects will test a CRISPR/Cas9-based gene therapy for Angelman syndrome in mice and human neurons. Zylka is the principal investigator for this project, which is funded by a $2.8-million grant from the National Institute of Neurological Disorders and Stroke.

See the full press release here

The ASF has been funding Dr. Zylka’s research into Angelman Syndrome since 2011, including his initial study into CRISPR/Cas9 in 2016

 

 

CBD May Alleviate Seizures
16 Sep

An ASF funded research study was published in BioRXiv and the Journal of Clinical Investigation.  See the press release below for more information and the outcomes of the study.  

 

CBD May Alleviate Seizures, Benefit Behaviors in People with Neurodevelopmental Conditions

UNC School of Medicine researchers led by Ben Philpot, PhD, and Bin Gu, PhD, found that cannabidiol had anti-seizure effects and behavior benefits in animal models of Angelman syndrome, a neurodevelopmental disorder.

 

Media contact: Mark Derewicz, 984-974-1915

 

CHAPEL HILL, NC – September 16, 2019 – A marijuana plant extract, also known as cannabidiol (CBD), is being commonly used to improve anxiety, sleep problems, pain, and many other neurological conditions. Now UNC School of Medicine researchers show it may alleviate seizures and normalize brain rhythms in Angelman syndrome, a rare neurodevelopmental condition.

Published in the Journal of Clinical Investigation, the research conducted using Angelman syndrome animal models shows that CBD could benefit kids and adults with this serious condition, which is characterized by intellectual disability, lack of speech, brain rhythm dysfunction, and deleterious and often drug-resistant epilepsy.

“There is an unmet need for better treatments for kids with Angelman syndrome to help them live fuller lives and to aid their families and caregivers,” said Ben Philpot, PhD, Kenan Distinguished Professor of Cell Biology and Physiology and associate director of the UNC Neuroscience Center. “Our results show CBD could help the medical community safely meet this need.”

CBD, which is a major phytocannabinoid constituent of cannabis, has already shown to have anti-epileptic, anti-anxiety, and anti-psychotic effects. And in 2018, the FDA approved CBD for the treatment of seizures associated with two rare forms of epilepsy, but little is known about the potential anti-seizure and behavioral effects of CBD on Angelman symptom.

The Philpot lab is a leader in the creation of genetically modified mouse models of neurodevelopmental disorders, and they use these models to identify new treatments for various diseases, such as Rett, Pitt-Hopkins, and Angelman syndromes.

In experiments led by first author Bin Gu, PhD, a postdoctoral fellow in the Philpot lab, the UNC-Chapel Hill researchers systematically tested the beneficial effects of CBD on seizures, motor deficits, and brain activity abnormalities – as measured by EEG – in mice that genetically model Angelman syndrome, with the expectation that this information could guide eventual clinical use.

The researchers found that a single injection of CBD substantially lessened seizure severity in mice when the seizures were experimentally triggered by elevated body temperature or loud sounds. A typical anti-convulsant dose of CBD (100 mg/kg) caused mild sedation in mice but had little effect on motor coordination or balance. CBD also restored the normal brain rhythms which are commonly impaired in Angelman syndrome.

“We’re confident our study provides the preclinical framework necessary to better guide the rational development of CBD as a therapy to help lessen seizures associated with Angelman syndrome and other neurodevelopmental disorders,” Gu said.

Philpot and Gu added that patients and families should always seek advice from their physician before taking any CBD products, and that a human clinical trial is needed to fully understand its efficacy and safety.

Other authors were Madison Glass, Marie Rougié, Viktoriya Nikolova, Sheryl Moy, PhD, and Paul Carney, MD, all of UNC-Chapel Hill.

 

The National Institutes of Health and the Angelman Syndrome Foundation funded this work.

ASF Honors Award Winners
05 Aug

ASF Honors Award Winners at the 2019 ASF Conference

At the 2019 ASF Scientific Symposium and Family Conference in Louisville, KY, the Angelman Syndrome Foundation recognized four people with special awards at the Family Conference Welcome Reception.  The board and staff of the Angelman Syndrome Foundation, as well as the entire community of families, teachers and scientists are grateful to these four individuals for their dedication and hard work. 

 

Harry & Audrey Angelman Award for Meritorious Service

Awarded to: Erin Sheldon

Erin Sheldon

Erin Sheldon has dedicated her life to supporting families on their communication journey. She is first and foremost a mother to Maggie. She is an advocate for inclusive schools and communities. She earned her Masters in Education studying the learning needs of students with complex disabilities. Erin has spend many years helping the Angelman Syndrome Foundation support families in their communication journey.  The Harry & Audrey Angelman Award for Meritorious Service is given to an individuals who has demonstrated a strong commitment to enhancing the awareness and understanding of Angelman Syndrome in their community. Erin lives this every day by working hard to be an advocate of children and adults with Angelman syndrome, as well as dedicating her life’s work to helping them find their voice!

 

The Dr. Claudia Benton Award for Scientific Research

Awarded to: Dr. Stormy Chamberlain

Stormy Chamberlain

Dr. Claudia Benton was passionate about the Angelman syndrome community. She had completed her pediatric neurology fellowship with Dr. Zoghbi and was in the process of her genetics fellowship with Dr. Beaudet when she died in 1998.  She was a wonderful, kind, and very dedicated person who loved the kids with Angelman syndrome that she worked with. The Claudia Benton award winner demonstrates a strong commitment to advancing the scientific knowledge as it pertains to Angelman Syndrome.  As well as an ongoing commitment to research that improves the understanding or treatment of Angelman Syndrome.  There is no one who is more deserving of this award than this year’s winner, Stormy Chamberlin.  Stormy Chamberlain is a widely published, 10-year researcher in the field of Angelman syndrome and UBE3A, who has given more than 30 talks and lectures about a variety of related topics. Dr. Chamberlain established her own lab at UConn in 2009, using induced pluripotent stem cells (iPSC) to model and study human imprinting disorders, focusing on Angelman syndrome, Prader-Willi syndrome, and Duplication 15q syndrome. She serves on the ASF Board of Directors as well as the Chair for the Scientific Advisory Committee.

“We are so thankful to Stormy for the dedication she displays for our children on a daily basis.  Knowing that they’re are individuals out there like Stormy working hard towards a cure for our kids is just the hope we need.”  Quote from a parent.

 

Lifetime Achievement Award

Awarded to: Eileen Braun

Eileen Braun

Eileen Braun served as the Executive Director of the ASF from 2004 until April 2019. Prior to that, Eileen worked as the special event coordinator for ASF 2001-2003, following her volunteer involvement from 1999-2001.

Some highlights from Eileen’s tenure as Executive Director:

  • Started the ASF Walk which, to date, has raised over $16M for research, family support, education and advocacy.
  • Prior to her tenure as Executive Director, ASF had invested a total of $275,000 on research. Since that time ASF has funded over $10M in research comprising over 100 individual projects, 61 different researchers, 40 different scientific institutions, and 7 different countries. Additionally, ASF spent about $6,000 in family support the year she took the reins and now ASF spends over $500,000 annually in support of the Angelman community.
  • In 2010 Eileen organized the first AS research road map designed to lay out the plan to organize research investment that would impact the clinical care of individuals with AS and, eventually, lead to a cure.
  • ASF developed and maintains the single largest AS registry in the world, including over 4,000 individuals with AS from all 50 states and over 80 countries around the world.
  • ASF developed a network of 8 US based clinics and 4 international clinics that specialize in the treatment for individuals with AS and are not serving as the hub for clinical research for AS related treatments.
  • During Eileen’s tenure, the ASF developed the ASF Resource Team, Communication Training Series, and the AS Behavioral Training Series.
  • ASF has hosted 8 family conferences and 11 scientific symposia.

Eileen dedicated her professional career to the cause of Angelman syndrome and there is nothing in the community without her fingerprints on it. Eileen was awarded the last ASF Lifetime Achievement Award and, the Board announced the creation of the Eileen Braun Lifetime Achievement Award.

 

Eileen Braun Lifetime Achievement Award

Awarded to: Dr. Art Beaudet

Dr. Arthur Beaudet

Dr. Beaudet received his M.D. from Yale, did pediatric residency at Johns Hopkins, and was a research associate at the National Institute of Health before joining Baylor College of Medicine (BCM) in 1971.  He is a well-known editor of the Metabolic and Molecular Bases of Inherited Disease textbook for the 6th through 8th editions; has served on many editorial boards and national review panels. He was President of the American Society of Human Genetics in 1998 and was elected to the National Academy of Medicine in 1995 and to the National Academy of Sciences in 2011.

Dr. Beaudet has made diverse contributions in the field of mammalian genetics including discovery of uniparental disomy in humans, identifying the Angelman syndrome gene, and publishing over 300 original research articles. Additionally, related to Angelman syndrome, his lab and another group identified UBE3A as the Angelman gene in 1997, and in 2015, his lab in collaboration with Ionis showed that oligonucleotides could be used to activate the paternal copy of the Angelman gene in mice, possibly opening a path towards treatment of AS.

Dr. Beaudet is currently the Henry and Emma Meyer Distinguished Service Professor in the Department of Molecular and Human Genetics at BCM and Texas Children’s Hospital in Houston.

 

 

Dr. Elizabeth Jalazo Named as Director of Clinical Integration
12 Jun

Angelman Syndrome Foundation (ASF) Creates New Director of Clinical Integration Position for their Expanding Clinical Network that Offers Comprehensive Care and Treatment for those with Angelman Syndrome (AS)

 

The Angelman Syndrome Foundation (ASF) has announced that Dr. Elizabeth Jalazo, a pediatrician at the University of North Carolina in Chapel Hill, will take on the new position of Director of Clinical Integration for the ASF.

In her role as the Director of Clinical Integration, Dr. Jalazo will oversee ASF’s Clinic Network which currently includes eight domestic and four international clinics. In this role, she will work with our current ASF Clinic Networks to ensure excellence as well recruiting new clinics to serve individuals with Angelman Syndrome.  Dr. Jalazo will also work to increase resources to accelerate the discovery and development of effective therapeutics that can prevent or reduce the core symptoms of Angelman Syndrome (AS). Primary efforts will target medical research, with a strong focus on neurological, psychopharamacological and clinical trials research. In her role as Director of Clinical Integration, Dr. Jalazo will also serve as the ASF spokesperson in responding to the needs of the organization and community regarding medical concerns, inquiries, and policies. In this capacity, Dr. Jalazo will act as a primary liaison between ASF and medical professional organizations working with children and adults with AS, and their families.

Amanda Moore, CEO of ASF, states, “We are thrilled that Dr. Jalazo is filling this new and vital position at the ASF.  Because of her unique background, and due to her own experience of having a child with AS, Dr. Jalazo is also able to support the ASF in advocacy efforts as they relate to the AS community.  She has provided expert testimony to the US Congressional Rare Disease Caucus about the importance of ending the diagnostic odyssey and ensuring access to appropriate genetic testing for children and families. Additionally, Dr. Jalazo has spoken at the FDA about the importance of newborn screening and the impact of timely diagnosis in rare disease. She is working closely with legislative advocates on Capitol Hill to ensure the needs of our community are being heard.”

Dr. Jalazo is a pediatrician at the University of North Carolina in Chapel Hill. She received her Bachelor of Science from UNC Chapel Hill and her Doctor of Medicine (MD) from Wake Forest University. She completed her pediatric residency at Johns Hopkins Hospital in Baltimore, MD. Following a research fellowship in academic pediatrics, Dr. Jalazo also served as the pediatric Chief Resident at Johns Hopkins. She practiced in the DC area caring for children with complex healthcare needs prior to moving back home to North Carolina with her family. She lives in Chapel Hill, NC with her husband and three children. Her middle daughter, Evelyn has Angelman Syndrome. She is currently a fellow at UNC in the Division of Medical Genetics and Genomic Medicine.

In welcoming Dr. Jalazo to the new ASF position, Moore says, “Besides her vast experience and clinical understanding of AS, Dr. Jalazo has a deep passion for caring for children with special healthcare needs. She has served on the Board of the Angelman Syndrome Foundation since 2017 and is excited, as we are, to serve the community in this new role moving forward.”

ASF Funded Research finds Critical Role of UBE3A
30 May

Role of UBE3A in the Developing Brain

Your ASF donations hard at work at UNC and Erasmus Medical Center in the Netherlands. This pivotal study demonstrated that UBE3A is most critical in the developing brain and plays a less vital role later on in life.

This is important in designing clinical trials and knowing when is the best time to treat. But what does this mean for our loved ones? “This means that while developing a therapy that permanently reinstates UBE3A might be optimal, even a treatment that gives back UBE3A during critical periods of brain development could be truly transformative!” – Ben Philpot, PhD University of North Carolina at Chapel Hill

See the article in Molecular Autism.

ASF AS Clinic at UNC Chapel Hill Studies Anxiety
30 May

Anxiety in Angelman Syndrome

Important work coming out of the ASF Clinic Network at the University of North Carolina at Chapel Hill. Did you know that anxiety concerns are reported in 40% of people with AS? Characterizing that anxiety is critically important to design tools that can tell us if therapeutics are working!

Read the published paper. 

Thank you to all of our families who visit the clinics and make this research possible! And thank you to all of those generous donations that make our clinics possible. 

Roche, Biogen and Ionis Announce Collaborative Research Partnership
20 May

Roche, Biogen and Ionis logos

See the following announcement from May 16, 2019.

Also, see a Q&A on this collaboration for more details.  

 

Dear Angelman Syndrome Community,

We, Roche, Biogen and Ionis, are amongst several companies working towards finding potential treatments for Angelman Syndrome (AS). While Roche and the Biogen/Ionis team have two independent research programs, we all share the common goal of bringing potential new therapies for AS into clinical trials in the future. Improving the understanding of AS is a very important step in the drug development process, and AS families are at the center of our efforts. We are writing this letter to share with you an update on some of our current work in AS.

Today, we announce our collaborative research partnership on two new studies that will improve the understanding of AS and guide the design of future drug studies:

One study is called the AS CSF and Biomarker Study and is led by Biogen. The aim is to find potential biomarkers, biological signs of disease, that can be measured in CSF (cerebrospinal fluid, which is the fluid around the brain and spinal cord). These biomarkers could then be used to check if a drug has an effect on AS.

The other study is called the AS Endpoint Study, and is led by Roche. The aim is to find ways to measure disease impact in the home and clinic, and use new technologies to learn about AS. These measurements (endpoints) and technologies focus on areas such as sleep, communication and brain activity.

These two studies do not involve any drug. Their purpose is to help design possible drug trials for AS in the future. The specific goals of these studies have not been covered before by other observational studies in AS. These studies are expected to start in the second half of 2019. More information will be available on ClinicalTrials.gov when the first sites are opened. We will let you know as soon as this information is available. 

Families will be able to join one or both of these studies, and they can also be part of other non-drug studies such as the FDA funded Natural History Study at the same time. As you may already know, gathering natural history data in Angelman Syndrome patients is a critical component to understanding the disease. To design the best clinical study for a treatment, we need to better understand the disease progression in the absence of a treatment. Taking part in non-drug studies typically does not prevent someone from taking part in any studies involving an investigational drug in the future, as long as the individual matches the inclusion criteria for a future drug study.

Our companies are working together on these two new studies, in collaboration with researchers and families in the Angelman community, so that important scientific information on AS is collected and shared. In parallel to these non-drug studies, our companies continue to independently research potential drug candidates for future clinical studies.

We are very grateful to all families who volunteer to take part in research and drug development efforts. Only with your support can we advance potential therapies towards clinical trials. We look forward to enhancing our partnership with the community by providing regular updates on the status of these studies and our independent programs.

Sincerely,
The Roche, Biogen and Ionis Teams

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