Israel’s Angelman community is bringing hope to families worldwide

The Angelman Clinic at the Sheba Medical Center and the Israeli Angelman Syndrome Foundation are working closely at the forefront of advances in treating and managing this rare disease.

Gil Shay, who has Angelman Syndrome, with her carer Nigora. (photo credit: RUTI ALON)
Gil Shay, who has Angelman Syndrome, with her carer Nigora.
(photo credit: RUTI ALON)
For families of children diagnosed with severe disabilities, one of the most precious resources is one of the most overlooked: hope. But hope is exactly what’s on offer to the families of those diagnosed with Angelman Syndrome (AS) in Israel, thanks to the combined efforts of the Israeli Angelman Syndrome Foundation and the Angelman Clinic at the Sheba Medical Center r at Tel HaShomer.
Together they have turned Israel into a global center of excellence for AS, placing the Jewish nation at the forefront of recent breakthroughs in medical science which are bringing hope to so many families.
The clinic was the first center of excellence on AS outside of North America to become an accredited member of the Global Angelman Syndrome Clinic Network, and the first outside of the US to take part in successful clinical trials for drugs to alleviate the symptoms of the disease.
Both the foundation and the clinic were borne out of a recognition eight years ago from parents and physicians alike that too little information and expertise was being offered to carers of those affected with AS in the country.
AS is a neurological genetic disorder causing global developmental delay. Affecting around 1 in 15,000 people, those with the condition are unable to speak and require lifelong care. It also causes problems with movement and balance, seizures and sleep disorders. Unlike many genetic disorders which are inherited, the majority of cases of AS are caused by single gene deletion or mutation which manifests randomly, meaning that the syndrome is found equally across populations worldwide.
For Eitan Shay and his wife Tamar, the diagnosis of their daughter Gil with AS in 2013 was a blow.
“We started to learn about it and tried to get to a physician who would know what to do, and we weren’t really able to find anything, anybody to talk to, any information in Hebrew or in English and not any physician who can tell us about it,” Shay told The Jerusalem Post.
“So we had no one to talk to and we couldn’t find someone to treat Gil.”
The Shay family (photo: courtesy Eitan Shay)
The Shay family (photo: courtesy Eitan Shay)
Their search eventually led them to Dr. Gali Heimer at the Sheba Medical Center. The center was already home to a clinic for Rett Syndrome, at which patients are able to access a range of specialists and therapeutics all on the same day. In addition to the obvious benefit to carers in terms of ease of access, the clinic also benefits the professionals, as by seeing so many patients with the same condition they become expert in the nuances of the disease.
“I was treating approximately 15 patients [with AS] who were coming sporadically, and I thought that they deserved the same expert treatment that we were giving to the Rett patients,” Heimer told the Post.
The Angelman Clinic at Sheba was set up by Heimer and her colleagues in 2012, with the Israeli Angelman Foundation run by Shay following not long after. Since then, both organizations have gone from strength to strength.
The clinic now has 85 patients enrolled making it the fourth largest worldwide. Only two clinics in America and one in the Netherlands see more patients. Heimer’s patients range in age from one year old to 50.  The foundation, meanwhile, is in regular contact with around 100 families affected by AS. Being in close contact with the clinic means that when a child is newly diagnosed, the foundation can reach out to them immediately to offer support.
This hand-in-glove contact between the professionals and families is causing Shay to rethink his initial conceptualization of the clinic and the foundation as being entirely separate.
“There are [currently] two entities: the foundation and the clinic, but I see it as an infrastructure combined over a very large group of families who we are able to connect through the parents’ organization,” he said.
It is precisely that infrastructure which presents such a golden opportunity to research and development companies looking into potential therapeutics for AS.
“We can get messages out really fast and we can get feedback really fast. These things become very important when you want to get to large operations such as [those running] clinical trials,” Shay said.
“So there are the families, there is the foundation, and this is connected to the clinic which is unique. Everybody goes to the same clinic; it’s located in a sophisticated medical center. Everybody is also a maximum of three hours’ drive away so you don’t have to fly over or sleep over. All of these things are critical when considering clinical trials.”
In 2018 the clinic took part in the Phase 2 STARS clinical trial to test OV101 (gaboxadol), a novel drug developed by New York-based Ovid Therapeutics to treat the symptoms of AS by tackling the underlying pathology of the disease. Ten of the 88 participants in the trial were located in Israel, with the remainder in America.
“This was my dream, to bring the most novel therapeutics to my patients the minute they are available,” Heimer said.
“We’ve already managed to do that with OV101, we’ve participated both in the phase 2 STARS trial for adolescents and adults, and we’re now participating in the extension trial for adults and adolescents, and the Neptune trial for the pediatric community.”
In doing so, Heimer has proved that her clinic is capable of carrying out the rigorous data collection requirements of a clinical trial.
“I don’t know if Gali told you this,” Shay confided to the Post, “but Ovid was highly impressed with Gali and her professionalism, and with the medical center’s ability to conduct clinical trials and gather data. Everything is considered very sophisticated.
“Not only did Ovid carry out the trial here, which was the first outside the US for AS, but they were very impressed and happy with the way it was done.”
That success has allowed Shay to promote Israel as a center of excellence for other companies looking to carry out clinical research into therapeutics for AS.
“We try to keep in contact with every company and researcher studying Angelman Syndrome,” Shay said. “In recent months, momentum has been shifting more towards the pharma companies, so naturally we are shifting the same way.
“Beyond North America, Israel is almost the only site that has the knowledge and expertise to conduct trials,” he added. “So if anyone is looking outside of US and Canada to conduct clinical trials it is very likely that we’ll be discussing that with them.”
2020 is set to be another big year for the Angelman community as the first results from the Neptune trial should be coming through this summer. Ovid hopes the results will offer support for its New Drug Application, filed with the US Food and Drug Administration, providing a pathway to get the drug on the market.
“It’s my hope that OV101 will be covered by the Israeli health basket, because it really improved many of the symptoms and increased quality of life for both the patient and family,” Heimer told Angelman Syndrome News in September.
Meanwhile, Saturday was International Angelman Day, when the Angelman community worldwide joins together to raise awareness of the syndrome and forge connections in support of one another.
This year, Shay and a representative from the Italian Angelman Syndrome Foundation were asked by the Angelman Syndrome Alliance (ASA), an international network which directs grant monies globally into AS research, to brainstorm ways to raise awareness of AS.
“We came up with the idea to create a frame that can be added to people’s profile pictures on their Facebook account. It’s very easy, and for me, this is why I loved the idea, because once you add the frame, all your friends on Facebook can see it and ask you about it, and want to do the same.”
Shay hopes the frame, which can be added with the click of a button, will provoke conversations around AS. The frame carries the logos of ASA and International Angelman Day, “but we also worked with local organizations so everybody has their own logo, so there are several frames wandering around on Facebook,” he said.
With so much going on, those conversations are sure to be very exciting – and very hopeful – indeed.