Courtesy of Sean McCabe

Meghan Edberg is the mother of five-year-old named William. About three years ago, when William was nonverbal and started exhibiting developmental delay, genetic testing confirmed that he had Angelman Syndrome, a rare neurogenetic disorder affecting 150,000 individuals worldwide. Neurodegenerative disorders are a bleak spot in medicine, with no treatments currently available, but with new breakthrough research, a cure may be on the horizon.

At the forefront of the battle against Angelman Syndrome is Professor and Chief of Medical Genetics Yong-Hui Jiang’s lab in collaboration with international parent advocacy organization Foundation for Angelman Syndrome Therapeutics, which has fundraised $5.8 million toward a cure — $800,000 of which has gone to Jiang’s lab. On March 31, School of Medicine researchers came together with FAST affiliates to look toward the future of a cure against Angelman Syndrome. 

“We want to go back to our donors and say, ‘Hey, we were at Yale, we saw and heard from the researchers and saw the work being done, and we stand by it.’” Edberg — FAST director of community engagement — said in an interview with the News. “We want to tell them ‘We believe it and we need your help for our loved ones, to be able to have a more promising future.’”

Angelman Syndrome is caused by silencing of the maternal chromosome’s UBE3A gene, usually by its deletion or mutation. Current research seeks to rescue the maternal gene, as well as to re-express the paternal version of UBE3A, which is otherwise suppressed. Three therapies for Angelman Syndrome are currently undergoing clinical trials, one of which is funded by FAST, to temporarily prevent paternal silencing. More critically, FAST’s goal is now to “make the technology permanent,” according to Allyson Berent-Weisse, chief science officer at FAST. 

“The data in the permanent solution is almost more promising than anything else we’ve ever seen,” Berent-Weisse said in an interview with the News. 

The day-long event on March 31 invited FAST’s top fundraising families, all of whom are parents with children who live with Angelman Syndrome, from across the country to experience firsthand the impacts of their donations — and glimpse the hope on the horizon. Fundraisers, FAST board members, Jiang lab members and Yale collaborators came together to witness and learn about ongoing research. 

The agenda opened at the Stem Cell Center, where invitees watched and participated in a Jiang lab meeting and discussion. Presentations by Associate Research Scientists Xiaona Lu, Kun-Yong Kim and Yunhua Bao underscored new research findings within and outside the Jiang lab. The lab members debated the merits of a paper presented by Kim, positing a novel CRISPR method, while parents interjected with questions and ideas.

“[This is] the combination of amazing, committed parents who believe in a cure for their kid and amazing, committed scientists who … are discovering those cures,” Berent-Weisse told the News. “[We’re] putting it all together in a way that’s digestible, logical and strategic, to make it all work.”

The lab meeting was followed by a tour of the Giraldez and Jiang labs, both of which collaborate on Angelman Syndrome research, as well as a walk around the Zebrafish Phenotyping Core — a facility containing 1500 tanks of zebrafish in which human diseases can be modeled. The FAST families noted appreciation and excitement about witnessing “science in action.”

“To be able to see all of the details that go into the scientific process to get these therapies from the lab to humans … is eye-opening,” Edberg said. 

For Jiang, the event was inspiring both personally and academically. Twenty-five years prior, during his doctoral training at Duke University, Jiang had created the first animal model for Angelman Syndrome. Due to limited knowledge and resources at the time, however, research into Angelman’s Syndrome came to a standstill.

Now, Jiang points to rapid advancements which have made possible a formerly elusive cure. He noted that his lab’s progress has been “miraculous.”

“Sometimes scientists just come to the perfect time, perfect location, perfect people,” Jiang said. 

One of these “perfect people” includes Lu, who had originally been a craniofacial plastic surgeon, operating on children with abnormal skull fusions. But these anatomical treatments were painful and insufficient, Lu said, as she recalled having to perform surgeries again and again as the children grew up. 

“You cannot cure this patient’s sickness, no matter how many surgeries you put on them,” Lu said. “I wanted to start with a genetic way to cure these young babies from the very beginning … so [that] when they are born, they won’t suffer so much.” 

Today, Lu is one of the lead researchers against Angelman Syndrome in Jiang’s Lab. She generates mouse models with different manifestations of Angelman Syndrome — some of which take generations and generations to breed, according to her lab meeting presentation. As Lu shared during the March 31 meeting, she has been able to rescue these Angelman-afflicted adult mice from their gene deletions via genome editing — a critical step toward a cure, which she hopes can soon be replicated in larger animals.

Edberg noted her gratitude for the work and motivation of Jiang’s lab. Even though Jiang works as a physician-scientist, interacting with patients with Angelman Syndrome in the clinic, neither he nor his lab members have children with Angelman Syndrome. 

“Seeing these incredible researchers have a passion, without necessarily having a child with Angelman Syndrome, is truly touching,” Edberg said. “It’s not just driven by publications or egos or status. Everyone’s really here for the right reasons.”

In her closing remarks, Berent-Weisse also noted the importance of research driven by “children not mice.” As a fundraising gift, the FAST members presented the lab members with a fundraising gift — a photobook with pictures of all their children. 

Even as Lu and Jiang debated new data arising from Lu’s mice, and as lab members and parents alike considered new ways to deliver the best molecular target treatment, Jiang emphasized his patient-centered research approach above all.

“After you interact with these patients and their families, you realize, ‘Oh my goodness, my research becomes so critical,’” Jiang said. “We’re going to change people’s lives.”

FAST was founded in 2008.