Category Archives: Uncategorized

LADDER Database
25 Nov

LADDER Database

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.

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

Zylka Lab at UNC awarded $6.1 million from NIH

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

 

 

ASF Honors Award Winners
05 Aug

ASF Honors Award Winners

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.

 

 

Angelman Syndrome Foundation Expands Clinic Network Internationally
06 Dec

Angelman Syndrome Foundation Expands Clinic Network Internationally

Comprehensive Clinics Provide Unique Support for Individuals with Angelman Syndrome in Canada and Israel

AURORA, Ill. (December 6, 2018) – The Angelman Syndrome Foundation (ASF) expands its Angelman Syndrome Clinic Network through collaboration with international partners: The Children’s Hospital of Eastern Ontario in Ottawa, Canada, and the Edmond and Lily Safra Children’s Hospital of the Sheba Medical Center near Tel Aviv, Israel. With the addition of these clinics, the ASF Angelman Syndrome Clinic Network has grown to 10 locations globally, including eight locations across the U.S.

The ASF Angelman Syndrome Clinic Network is the first and only resource of its kind for individuals with Angelman syndrome (AS) and their families. Founded by the ASF, it leverages partnerships with leading medical and research institutions to provide individuals with AS the comprehensive care they need from infancy through adulthood.

As part of the commitment to improving the lives of patients and families living with AS, the medical teams of the ASF AS Clinic Network also participate in the latest clinical research protocols and trials. And, the ASF AS Clinic Network is currently developing the first standards of care in AS.

“The ASF AS Clinics provide vital, life-changing – and often life-saving – care for our children of all ages. No other resource like this exists for AS families, so to broaden the network internationally is critical for families around the world,” said Eileen Braun, executive director of the Angelman Syndrome Foundation and mother to a young woman with AS. “The ASF AS Clinics also provide a pivotal platform for clinical research sites with experienced clinicians. The knowledge base and clinical data provided by the ASF AS Clinic Network is imperative to move research forward, from study design to implementation through clinical trials.”

The purpose of the ASF AS Clinic Network is to reduce the frequency and severity of AS symptoms that interfere with function, such as seizures, behavior and sleep problems. In addition, the clinics work with families to develop educational recommendations to optimize educational programming for individuals with AS, thus helping these individuals achieve their full developmental potential. 

“Partnering with ASF to become part of the global AS Clinic Network has created incredible collaboration and information sharing,” said Jane Summers, PhD, Psychologist, and Dr. Erick Sell, MD, Pediatric Neurologist, co-founders of the ASF AS Clinic at the Children’s Hospital of Eastern Ontario. “This has helped us tremendously to provide the exceptional, expert care for our patients with Angelman syndrome that we are committed to delivering.”

With the ultimate goal of improving quality of life for individuals with AS and their families, the ASF AS Clinic Network provides comprehensive access to experts who specialize in AS. These AS experts include neurologists, epileptologists, developmental-behavioral pediatricians, psychologists, sleep medicine physicians, rehabilitation medicine specialists, gastroenterologists, pulmonologists, speech language pathologists, physical/occupational therapists, genetic counselors, social workers and nutritionists.

“Knowledge and experience sharing are highly important, especially in the field of rare disorders such as Angelman syndrome,” said Dr. Gali Heimer, MD, PhD, Pediatric Neurologist and the Head of the Safra Children’s Hospital Israeli Angelman Syndrome Clinic. “We are honored to join the global ASF AS Clinic Network. I am certain that this collaboration will contribute significantly to the quality of care that AS patients receive worldwide, and it will also aid and facilitate AS-related clinical trials and the search for specific novel therapeutics for this disorder.”

The Safra Children’s Hospital Israeli Angelman Syndrome Clinic within the Sheba Medical Center in Tel Hashomer, near Tel Aviv Israel, was established in partnership and operates in full cooperation with the Israeli AS Foundation.

“Ever since the Israeli AS Foundation was established, we have set it as one of our major targets to cooperate, share information and knowledge, and be as in sync as possible with AS parents’ organizations, physicians and researchers worldwide,” said Eitan Shay, CEO of the Israeli AS Foundation and father to an 8-year-old girl with AS. “We are proud and honored that our long-term and warm relationship with the ASF has led to this highly important step of the Safra Children’s Hospital Israeli AS Clinic joining the ASF AS Clinic Network.”

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ABOUT ANGELMAN SYNDROME (AS)

Occurring in one in 15,000 live births, Angelman syndrome is a neurogenetic disorder often misdiagnosed as autism or cerebral palsy – that causes severe neurological impairment, appears in newborns and lasts for a lifetime. During fetal development, the loss of function of a particular gene in the brain occurs, resulting in neurons functioning improperly and causing deficits in development. Individuals with AS experience developmental delay, lack of speech, seizures, walking and balance disorders, and typically exhibit a happy demeanor characterized by frequent smiling, laughter and excitability.

ABOUT THE ANGELMAN SYNDROME FOUNDATION (ASF)

The Angelman Syndrome Foundation’s mission is to advance the awareness and treatment of AS through education and information, research, and support for individuals with AS, their families and other concerned parties. The ASF sponsors AS research through grants to researchers pursuing treatments and a cure for AS. Since 1996, the ASF has funded 101 research grants totaling more than $9.5 million. The ASF has awarded a majority of these funds ($9.2 million) beginning in 2005.

ABOUT CHEO

Dedicated to the best life for every child and youth, CHEO is a global leader in pediatric health care and research. Based in Ottawa, CHEO includes a hospital, children’s treatment center, school and research institute, with satellite services located throughout Eastern Ontario. CHEO provides excellence in complex pediatric care, research and education. We are committed to partnering with families and the community to provide exceptional care — where, when and how it’s needed. CHEO is a founding member of Kids Health Alliance, a network of partners working to create a high quality, standardized and coordinated approach to pediatric health care that is centered around children, youth and their families. Every year, CHEO helps more than 500,000 children and youth from Eastern Ontario, western Quebec, Nunavut and Northern Ontario.  

ABOUT THE SAFRA CHILDERN’S HOSPITAL 

The Edmond and Lily Safra Children’s Hospital of the Sheba Medical Center is a university-affiliated tertiary referral center located near Tel Aviv, Israel. It is renowned for its compassionate care and cutting-edge medicine, state-of-the-art facilities and dedication for advancing research of pediatric disorders. It specializes, among other things, in the care and research of rare disorders and holds the national clinics of many of those such as Rett, Ataxia Telangiectasia, Tuberous Sclerosis, Fragile X and of course, Angelman Syndrome. As part of the hospital’s vision of providing holistic care to patients and their families, the rare disorders clinics provide multidisciplinary expert services scheduled all for the same day and a continuity of care into adulthood. The Safra Children’s Hospital offers its expert services not only to patients from all across the country, but also the Palestinian Authority, and the Mediterranean and Near East regions.

 

MEDIA CONTACT

Allison Dukes, Dalton Agency
Mobile: (608) 616-2713
Email: adukes@daltonagency.com

 

Highlights from the 2018 Angelman Syndrome Foundation/Dup15q Research Symposium
17 Aug

Highlights from the 2018 Angelman Syndrome Foundation/Dup15q Research Symposium

Attendees Share Highlights from the 2018 Angelman Syndrome Foundation/Dup15q Research Symposium

The most brilliant minds in Angelman and Dup15q syndromes collaborated for two days in Chapel Hill, North Carolina last week, sharing unpublished data and knowledge that is pushing the AS community closer toward treatments and a cure for AS.

As the leading AS research meeting in the world, the ASF/Dup15q Research Symposium left each attendee—ranging from seasoned scientists and AS clinicians to post-docs and graduate students, who are all passionate about AS—inspired and super-charged to further their work in AS.

 

Several attendees from different backgrounds have shared their key insights from the ASF/Dup15q Research Symposium:

Dr. Steven Siegelbaum
Dr. Steven Siegelbaum
Chair, Department of Neuroscience, Columbia University Medical Center
Grandfather to a 3-year-old boy diagnosed with Angelman syndrome

“As both a neuroscientist…and as a grandfather with a 3 year old grandson with AS, I found the meeting to be extremely informative. It appears that the field is at the cusp of developing both useful small molecule therapeutic approaches to treat some of the symptoms of AS (and Dup15q) and gene therapeutics to correct the underlying loss of Ube3a in AS. Because AS is clearly associated with pleiotropic effects on underlying neural function (e.g. alterations in neural structure, tonic inhibition, axon diameter, ion channel expression) and pleiotropic behavioral changes (cognitive function, sleep, motor development, language), I think it will be important in the future to gain a clearer understanding of the relation between the two. I believe the expanded use of MRI in individuals with AS and Dup15q will be important to correlate alterations in brain structure (including white matter loss) with behavior and with treatments, and to relate findings in humans to results in mouse models.”

 

 

Stormy Chamberlin
Dr. Stormy Chamberlain
ASF Scientific Advisory Committee Chair
Associate Professor, Dept. of Genetics and Genome Sciences, UConn Health

“Here are my top three key takeaways from the Symposium:

  1. We have a lot of work going on in clinical space including trying to identify measurable features to be used as outcome measures/biomarkers for upcoming clinical trials. This truly shows how far and quickly the science and understanding of AS is advancing. Attendees even made comments about how many clinicians from many specialities presented, which is great!
  2. I was impressed by the presentations about new, novel ways to modulate RNA that might be helpful for Angelman syndrome—they used approaches that haven’t been thought of before for AS. It was a perfect example of people thinking outside of the box, and how we can apply other learnings to AS to solve issues with Ube3a.
  3. Overall, there was a tremendous amount of resource and information sharing. People are truly coming to this meeting to learn, network and collaborate, and they are sharing work that is yet unpublished—but highly advanced and important to finding treatments and a cure for AS. This includes the sharing of information from the Angelman Syndrome Clinics, which is impressive data. The collaboration was evident in a nearly all presentations, and it is truly amazing. I am so grateful for where we are, and for where we are going!”

 

 

Rossella Avagliano Trezza


Rossella Avagliano Trezza
Post-doc in ASF-funded researcher Dr. Ype Elgerma’s lab

“The ASF/Dup15q Research Symposium was a very stimulating experience, it’s amazing to see how the clinical and scientific worlds come together to deepen the knowledge on these disorders and broaden our horizons. As Ben Philpot mentioned in his closing remarks, much progress has been made in the past three to five years and this conference highlighted some of the most interesting findings. Even though I truly believe any contribution to the meeting is instrumental to move our research forward, I think a few key talks made the real difference:  

  • Targeting and eliminating RNA in RNA disorders: RNA editing is transient which in terms of a specific targeting is a great advantage. 
  • Measurable parameters to determine altered morphology in human-induced pluripotent stem cell (iPSC)-derived neurons: As science progresses further, it’s more and more evident the need for biological systems that mimic the human brain. While we are far away from generating a faithful representation of a human brain in vitro, iPSC-derived neurons offer a very close approximation. The work of Judy Bloom and Stormy Chamberlain is in this sense an essential outcome measure.
  • The comparison between Christianson and Angelman syndromes: I have always found fascinating the possibility of finding new Ube3a interactors via Angelman-like disorders, and current research that is focusing on common aspects in the pathophysiology and cellular biology of both Angelman and Christianson syndromes is incredibly interersting.

Overall I think these type of symposia where the top scientists of the field have the possibility of talking and sharing ideas are the true fuel of scientific research. There is no progress without confrontation and the ASF/Dup15q conference allowed just that.

Positive Topline Data from Phase 2 STARS Trial of OV101 for the Treatment of Angelman Syndrome
06 Aug

Positive Topline Data from Phase 2 STARS Trial of OV101 for the Treatment of Angelman Syndrome

Positive Topline Data from Phase 2 STARS Trial of OV101 for the Treatment of Angelman Syndrome

— OV101 achieved primary endpoint of safety and tolerability —
— Robust and statistically significant improvement (p=0.0006) in the first prespecified efficacy endpoint(CGI-I) observed at 12 weeks of treatment in once-daily dose group compared to placebo —
— STARS data support plans to advance OV101 development and discuss with regulators next steps for a registrational pathway —
— Conference call and webcast today at 8:00 a.m. EDT —

NEW YORK – August 6, 2018 – Ovid Therapeutics Inc. (NASDAQ: OVID), a biopharmaceutical company committed to developing medicines that transform the lives of people with rare neurological diseases, today announced that the Phase 2 STARS trial of OV101 achieved its primary endpoint of safety and tolerability. The investigational medicine showed a favorable safety profile and was well tolerated in adults and adolescents with Angelman syndrome. OV101 is the only selective extrasynaptic GABAA receptor agonist in development shown to mediate tonic inhibition, a key underlying pathophysiological mechanism of Angelman syndrome. Ovid’s founder, president and chief scientific officer, Matthew During, M.D., DSc,FACP, will present the data today at the 2018 Angelman Syndrome Foundation/Duplication15q Research Symposium in Chapel Hill, North Carolina.

The Phase 2 STARS international study is the first industry-sponsored, randomized, doubleblind,placebo-controlled clinical trial for Angelman syndrome. The study randomized 88 patients across three groups: a once-daily or twice-daily dose of OV101 or placebo. At the prespecified efficacy analysis at 12 weeks of treatment, OV101 showed a statistically significant improvement compared to placebo in the physician-rated clinical global impressions of improvement (CGI-I) – a measure commonly used in clinical trials that allows the physician to capture a constellation of clinical symptoms. CGI-I was ranked first in the topline statistical plan. Subsequent analyses in the hierarchy were conducted on a prespecified subset of scales across the domains of behavior, sleep and gait. While the analysis of these prespecified subsets did not show a statistically significant difference from placebo, full data analyses on these domains are ongoing and will be communicated in the future. Ovid intends to discuss these data with regulatory authorities to determine the next steps for a registrational pathway. Based on these data, the company plans to initiate in the fourth quarter of 2018 an open-label extension study (named ELARA); Angelman syndrome patients who completed any prior OV101 study may be eligible to receive the investigational medicine in this study.

Angelman syndrome is a rare, lifelong, genetic disorder that affects 1 in 15,000 people in the U.S. It is characterized by severe impairment in behavior, learning, verbal communication, motor skills, and sleep, and there are no FDA-approved medicines or an established treatment paradigm for this condition. If approved, OV101 could be the first medicine to specifically target a key underlying neurological dysfunction of Angelman syndrome — impaired tonic inhibition that is most commonly caused by a disruption of the UBE3A gene.

“We are excited by these data, as this is the first demonstration of positive clinical effect on overall symptomology in Angelman syndrome,” said Jeremy Levin, DPhil, MB, BChir, chairman and chief executive officer of Ovid Therapeutics. “In collaboration with the Angelman community, we designed a robust study to evaluate prespecified endpoints that may pave the way for a registrational pathway for a disorder that has no previously approved medicines. These data are a tribute to the patients and their families and we thank them.”

“These initial data from the STARS study are encouraging, particularly the statistically significant improvement in overall symptoms that we see in the CGI-I scale in the once-daily dosing group. Angelman syndrome is a complex disorder and the CGI-I scale captures the totality of global neurological deficits and helps to define the impact of medicines on the individual and their families,” said Ron Thibert, D.O., MsPH, chairperson, STARS clinical trial steering committee, director, Angelman syndrome clinic at Mass General Hospital for Children, and assistant professor at Harvard Medical School. “The data reported today are the first data in Angelman syndrome to show a compound specifically targeting the syndrome having a clinical effect. Ovid is the first company to have conducted a double-blind, placebo-controlled study in Angelman syndrome, providing important clinical and scientific data. Based on these data, I believe OV101 has the potential to offer a clinically meaningful benefit specific to people living with Angelman syndrome.”

“The STARS study was designed to provide information to allow us to progress the development of OV101,” said Amit Rakhit, M.D., MBA, chief medical and portfolio management officer of Ovid Therapeutics. “With these findings, we have advanced our understanding of relevant endpoints to evaluate key symptoms of Angelman syndrome. Furthermore, we demonstrated that a once-daily dose of OV101 could be sufficient to drive clinically meaningful benefit to patients. We look forward to discussing the data with regulatory authorities to inform our future development plans.”

STARS Phase 2 Topline Data Summary and Design
STARS was a 12-week, double-blind, placebo-controlled Phase 2 study. Eighty-eight patients (adults, n=66; adolescents, n=22) aged 13 to 49 years of age diagnosed with Angelman syndrome were randomized at 13 clinical trial sites in the U.S. and Israel. The study randomized patients to one of three arms: once-daily (QD) dose of OV101 at night (15mg), twice-daily (BD) dose of OV101 (10mg in the morning and 15mg at night), and placebo.

The intent to treat (ITT) population was 88 patients. A modified intent to treat (mITT) analysis of 87 patients (mean age = 22.6), which includes any patient who enrolled in the study and received at least one dose of study drug, was performed to evaluate the efficacy endpoints.

The primary endpoint of the trial was to assess the safety and tolerability of OV101 compared to placebo. The STARS trial explored the clinical utility of OV101 on improvements in clinical global impressions, maladaptive behavior, sleep, and gross and fine motor skills.

Primary Endpoint: Safety and Tolerability Data
The study met its primary endpoint of safety and tolerability given that the adverse events (AEs) with OV101 treatment were similar to placebo treatment, with the majority of AEs being mild. OV101 showed a favorable risk profile and was well tolerated through 12 weeks of treatment. Overall, the data are consistent with the favorable risk profile observed in previous insomnia trials with this investigational medicine.

The most common AEs reported in the trial were vomiting, somnolence, irritability, aggression, and pyrexia.

Table 1: Most Frequent Adverse Events*

Table 1: Most Frequent Adverse Events

Events occurring in greater than 5 percent (two or more patients) compared to placebo in either treatment arm included pyrexia, rash, seizure, enuresis and myoclonic epilepsy.

Adverse Events Occurring More Frequently in OV101 Arms vs. Placebo

Serious adverse events (SAEs) of seizure were reported in two patients: one patient in the QD dose experienced a seizure and that was deemed unrelated to study drug; one patient experienced a seizure in the BID dose group and that was assessed as possibly related to study drug by the investigator.

Treatment discontinuations due to adverse events were low. One patient in the placebo arm discontinued compared to no patients and three patients in the once-daily dose group and twicedaily dose group, respectively.

  • Placebo arm: one patient with irritability
  • Twice-daily arm: one patient with myoclonus; one patient with seizure, and one patient with irritability/anxiety/sleep disorder

Efficacy Endpoint Data
At 12 weeks of treatment, the first prespecified efficacy endpoint (CGI-I) demonstrated a robust and statistically significant difference (p=0.0206; Fisher’s Exact test) between the combined OV101 treatment arms and placebo. This reflects an improvement in two-thirds of the combined treatment groups versus one-third in placebo.

Table 3: Response Based on CGI-I at Week 12; Comparison to Placebo

In the prespecified analysis using the rigorous Mixed Model Repeated Measures (MMRM), which evaluated each OV101 treatment arm independently against placebo, the difference in CGI-I mean score at 12 weeks was statistically significant (p=0.0006) in the once-daily OV101 group versus placebo and also in the combined OV101 treatment group versus placebo (p=0.0103).

Table 4: Mean CGI-I Symptoms Overall Score – by Dose Group at Week 12; Comparison to Placebo

In a post-hoc analysis of patients who were “much” or “minimally” improved having a CGI-I score of ≤3, the data suggest that younger patients who received a once-daily dose had the greatest response to OV101 compared to older age groups.

Table 5: Patients Who were ‘Much’ or ‘Minimally’ Improved in CGI-I Score (≤3) (Post-hoc Analysis)

Ovid Therapeutics plans to present the full clinical data from the STARS study at an upcoming medical meeting.

ELARA 1-year Extension Study
In the fourth quarter of 2018, Ovid expects to initiate ELARA, an open-label extension study that will enable individuals with Angelman syndrome who completed any prior OV101 study to be eligible to receive the investigational medicine. The study will use once-daily dosing and will assess long term safety and tolerability in addition to efficacy measures.

Ovid Therapeutics has created a website specifically to provide disease education on Angelman syndrome. Learn more at anglemansyndrome.com.

Conference Call and Webcast Information
Ovid Therapeutics will host a live conference call and webcast today, August 6, 2018, at 8:00 a.m. Eastern Time. The live webcast can be accessed by visiting the Investors section of the company’s website at investors.ovidrx.com. Please connect at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. Alternatively, please call 866-830-1640 (U.S.) or 210-874-7820 (International) to listen to the live conference call. The conference ID number for the live call is 8994338. A replay of the webcast will be available on the company’s website for two weeks following the live conference call.

About Angelman Syndrome
Angelman syndrome is a genetic disorder that is characterized by a variety of signs and symptoms. Characteristic features of this disorder include delayed development, intellectual disability, severe speech impairment, problems with movement and balance, seizures, sleep disorders and anxiety. The most common cause of Angelman syndrome is the loss of function of the gene that codes for ubiquitin protein ligase E3A (UBE3A), which plays a critical role in nerve cell communication, resulting in impaired tonic inhibition. Individuals with Angelman syndrome are highly social with a typical lifespan; however, they require constant support from a network of specialists and caregivers. Angelman syndrome affects approximately 1 in 15,000 people in the U.S. There are currently no U.S. Food and Drug Administration (FDA)-approved therapies for the treatment of Angelman syndrome.

Angelman syndrome is associated with a reduction in tonic inhibition, a function of the delta (δ)- selective GABAA receptor that allows a human brain to decipher excitatory and inhibitory neurological signals correctly without being overloaded. If tonic inhibition is reduced, the brain becomes inundated with signals and loses the ability to separate background noise from critical information.

About OV101
OV101 (gaboxadol) is believed to be the only delta (δ)-selective GABAA receptor agonist in development and the first investigational drug to specifically target the disruption of tonic inhibition, a central physiological process of the brain that is thought to be the underlying cause of certain neurodevelopmental disorders. OV101 has been demonstrated in laboratory studies and animal models to selectively activate the δ-subunit of GABAA receptors, which are found in the extrasynaptic space (outside of the synapse), and thereby impact neuronal activity through tonic inhibition.

Ovid is developing OV101 for the treatment of Angelman syndrome and Fragile X syndrome to potentially restore tonic inhibition and relieve several of the symptoms of these disorders. In preclinical studies, it was observed that OV101 improved symptoms of Angelman syndrome and Fragile X syndrome. This compound has also previously been tested in over 4,000 patients (over 1,000 patient-years of exposure) and was observed to have favorable safety and bioavailability profiles.

The FDA has granted Orphan Drug and Fast Track designations for OV101 for both the
treatment of Angelman syndrome and Fragile X syndrome. The U.S. Patent and Trademark Office has granted Ovid patents directed to methods of treating Angelman syndrome and Fragile X syndrome using OV101. The issued patents expire in 2035.

About Ovid Therapeutics
Ovid Therapeutics (NASDAQ: OVID) is a New York-based biopharmaceutical company using its BoldMedicine™ approach to develop therapies that transform the lives of patients with rare neurological disorders. Ovid has a broad pipeline of first-in-class medicines. The company’s lead investigational medicine, OV101, is currently in development for the treatment of Angelman syndrome and Fragile X syndrome. Ovid is also developing OV935/TAK-935 in collaboration with Takeda Pharmaceutical Company Limited for the treatment of rare developmental and epileptic encephalopathies (DEE).

For more information on Ovid, please visit http://www.ovidrx.com/.

Forward-Looking Statements
This press release includes certain disclosures that contain “forward-looking statements,” including, without limitation, statements regarding (i) timing and scope of any future clinical trials for OV101, (ii) the potential clinical benefit of OV101 to treat patients with Angelman syndrome, and (iii) the timing and results of any discussions with regulatory authorities regarding the registrational path for OV101. You can identify forward-looking statements because they contain words such as “will,” “believes” and “expects.” Forward-looking statements are based on Ovid’s current expectations and assumptions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that may differ materially from those contemplated by the forward-looking statements, which are neither statements of historical fact nor guarantees or assurances of future performance. Important factors that could cause actual results to differ materially from those in the forward-looking statements are set forth in Ovid’s filings with the Securities and Exchange Commission. Ovid assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

Contacts
Investors:
Lora Pike
Ovid Therapeutics Inc.
Senior Director, Investor Relations & Public Relations
lpike@ovidrx.com

Steve Klass
Burns McClellan, Inc
sklass@burnsmc.com
(212) 213-0006

Media:
Kelly Boothe, Ph.D.
W2O pure
kboothe@w2ogroup.com
(415) 946-1076

Elliot Fox
Group Director, Media Relations
W2O Group
efox@w2ogroup.com
(212) 257-6724

Healthcare Legislation in the US
18 Sep

Healthcare Legislation in the US

Statement Regarding Healthcare Legislation in the US

The Angelman Syndrome Foundation is issuing the following statement regarding healthcare legislation in the US because of its impacts on the lives of people with Angelman syndrome and their families.

Statement from Angelman Syndrome Foundation Board of Directors:

The healthcare proposals currently being debated in Congress include provisions that could have potentially devastating impacts on people with Angelman syndrome (AS) and their families. In support of people with AS and their caregivers, the Angelman Syndrome Foundation (ASF) strongly opposes any effort to cut or cap Medicaid, a program that provides vital services to children and adults with AS. Without sufficient Medicaid funding for home and community-based services, institutionalization would be the only viable option available to many of our loved ones with AS. Proposals to cut funding for school-based services funded by Medicaid and to eliminate affordable healthcare options for caregivers would have major impacts on our community as well. The Angelman community, including the ASF, is fighting for our loved ones with every tool we have. Please stand with us and contact your members of Congress to let them know why Medicaid and affordable healthcare are important to your family.

Facts:

  • Major national organizations including The Arc[1], The National Organization for Rare Disorders[2] and the National Down Syndrome Society[3] all oppose cuts and caps to Medicaid.
  • “Medicaid is the main source of funding for over 77% of the supports and services that individuals with intellectual and/or developmental disabilities (I/DD) use to live in the community.” (Source: ARC)[4]
  • “In 2017, 68 percent of school superintendents reported using Medicaid funds for school nurses, counselors, speech therapists, and other health professionals.”[5]

 


[1] http://www.huffingtonpost.com/entry/why-you-should-care-about-looming-medicaid-cuts_us_58a33332e4b0cd37efcfed80

[2]https://rarediseases.org/wp-content/uploads/2014/11/NORDs-Principles-for-Health-Coverage-Reform-Final.pdf

[3] https://www.ndss.org/About-NDSS/Newsroom/Recent-News/ndss-statement-on-bcra/

[4] https://blog.thearc.org/2017/05/11/passage-ahca-real-life-consequences-people-disabilities/

[5] https://blog.thearc.org/2017/05/11/passage-ahca-real-life-consequences-people-disabilities/

14 Aug

Published Paper: Microcephaly in AS Mice

Published Paper: Microcephaly in AS Mice

See the paper by Matthew Judson in The Journal of Neuroscience

Summary

Many individuals with Angelman syndrome (AS) have microcephaly—a smaller head and brain size—than typically developing individuals. This microcephaly is not present at birth, but becomes evident sometime during the first 18 months of life, indicating a problem with brain growth. During this early phase of development, the brain typically grows very quickly and must develop in a precise manner to support normal brain functions. In AS, the brain grows more slowly, and this correlates with developmental delay, impaired motor function, and EEG abnormalities. The ASF-funded research team, led by Ben Philpot, Ph.D., studied microcephaly in AS mice and sought to determine the cause of reduced brain size in the mice. The results were published in the August 2nd issue of The Journal of Neuroscience.

The team examined the brain growth of AS mice during early development and found that they develop microcephaly after birth. Although newborn AS mice have the same sized brains as their neuro-typical counterparts, the brains of AS mice grow more slowly, and are thus smaller than their neuro-typical littermates by the time they are juveniles. As with individuals with AS, this microcephaly persists into adulthood. Notably, Philpot’s group showed that changes in the amount of white matter accounted for most of the microcephaly in AS mice. White matter contains bundles of axons, which are the long, slender portions of neurons that transmit electrical signals to other neurons or muscles. Axons are coated with a substance called myelin, which acts to insulate the electrical activity of axons. Philpot and colleagues found that although the amount of myelin was normal in adult AS mice, the axons in AS mice were smaller in diameter than the mice without AS. These smaller axons correlated with deficits in nerve conduction in the AS mice. Future research will help determine exactly how the axon diameter deficit in AS mice arises during development, whether it might be related to delays in myelination, and how it could contribute to behavioral phenotypes.     

White matter deficits have been previously reported in individuals with AS. The ASF recently funded a collaborative group including Drs. Ben Philpot, Mark Shen, Heather Hazlett, and Ron Thibert to study this process in children and young adults with AS. Preliminary data from this work was presented at the Angelman Syndrome Foundation’s 2017 Research Symposium. More work in this important area of brain research is needed to determine if the white matter deficits observed in individuals with AS are caused by changes in axon diameter, as predicted by Philpot’s recent findings in AS mice. Importantly, if the extent of white matter structural deficits proves to correlate with the severity of impairments in nerve conduction and motor skills performance in individuals with AS, then measurement of white matter may serve as a helpful biomarker to gauge responsiveness to a potential treatment.

22 Jun

Development of Potential Outcome Measures for AS Clinical Trials

Angelman Biomarkers and Outcome Measures Alliance and Roche begin patient-centered qualitative research to inform potential outcome measures for Angelman syndrome clinical trials

Nashville, Tenn. (June 22, 2017) – A collaborative group of parent-driven organizations seeking a cure for Angelman syndrome has teamed up with F. Hoffmann-La Roche Ltd, (Roche), one of the world’s largest pharmaceutical and diagnostics companies, in the first phase of a study that will support the design of human clinical trials and treatment development for the disorder.

Roche has committed funding to create an Angelman syndrome conceptual model. Roche as a leader in personalized healthcare is taking a patient-centered approach to drug and treatment development.

According to Roche, the first phase of the study aims to better understand the impact of Angelman syndrome on patients and their families through interviews with caregivers and physicians around the world.

“The findings of this research will be a key step towards identifying and developing the best outcome measures and biomarkers for future clinical trials,” says Dr. Tom Willgoss, principal scientist, Roche.

 The study signals a new movement into the human testing phase of possible drug and therapy development for Angelman syndrome.

“To have such a cutting-edge biotech giant join all of us in the quest for a treatment and cure for Angelman syndrome is a very hopeful sign of significant movement for our families who struggle with the impact of this disorder,” says Dr. Allyson Berent, DVM, DACVIM, chief science officer for FAST (Foundation for Angelman Syndrome Therapeutics).

Dr. Stormy Chamberlain, chair of the scientific advisory committee for the Angelman Syndrome Foundation (ASF), agreed that this next phase of development in Angelman research takes a critical step in matching the needs of patients with Angelman syndrome to possible treatment and measurement strategies.

“We are all working together to determine the needs of families with Angelman syndrome in terms of new treatments and medications,” says Chamberlain.  

FAST and ASF joined efforts with Agilis Biopharmaceuticals to create the Angelman Biomarkers and Outcome Measures Alliance (A-BOM) in 2016. The alliance of foundations and biopharmaceutical firms works to help researchers identify the best ways to measure clinical progress in Angelman syndrome in an effort to design better trials to test the effectiveness of new experimental treatments. A-BOM is encouraging the families, caregivers and physicians of Angelman syndrome patients to participate in this effort by joining the Angelman registry. The registry assists researchers in collecting strategic information about the disorder from patients and their physicians. The registry can be found online at angelmanregistry.info.

“We need rigorous ways to measure how potential treatments may improve the quality of life for individuals with Angelman syndrome and their families,” says A-BOM’s director, Dr. Terry Jo Bichell. “Roche’s conceptual model will set a standard that will help researchers determine what to measure, how to measure it, and how to interpret their findings when they are trying to identify possible treatments.”

Initial findings for the first phase of the study are expected in 2017. The research team plans to interview the caregivers and clinicians of approximately 33 patients with Angelman syndrome in its sample.

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About The Angelman Biomarkers and Outcome Measures Alliance (A-BOM)

The Angelman Biomarkers and Outcome Measures Alliance (A-BOM) is a new group formed by both FAST (Foundation for Angelman Syndrome Therapeutics) and the Angelman Syndrome Foundation, together with researchers and pharmaceutical corporations to help move new treatments to the clinical trial phase. A-BOM includes scientists, foundations and corporations that are all working together to share in research, studies, trials and stories to help people with Angelman syndrome.