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When she was 2 years old, Magnolia “Maggie” Tesler, had hit all of her developmental milestones, but was starting to lose some of the words she learned in her young life. Nearly three years later, the Los Angeles girl has lost all power of speech, constantly hyperventilates, has difficulty walking and her body is in constant motion, but her family is holding on to the possibility of a cure for her diagnosis, Rett syndrome.
Rett syndrome is a neurodevelopmental disorder caused by random mutations in the MECP2 gene, which is also the name of the protein the gene makes. The diagnosis is almost exclusively made in girls, with symptoms appearing in toddlerhood. Rett is characterized by loss of hand function, distinctive hand movements, slowed brain and head growth, problems with walking, seizures and intellectual disability, according to the National Institutes of Health (NIH). It is not an inherited genetic disorder and the mutation occurs randomly. The disorder affects one in every 10,000 to 15,000 live births, according to NIH estimates.
For AJ and Jenny Tesler, the most important thing they can do for the care of their daughter is keeping her strong and healthy until a cure is found.
“She’s locked inside her body and all we’re trying to do is help her get out,” AJ, 37, told FoxNews.com. “We know that someday it’ll all be OK, but we need fundraising in order to make sure that happens.”
The Teslers and other families affected by Rett are optimistic not only because it is a single gene disorder— compared to disorders like autism that affect multiple genes— but also because research has shown that it can be reversed.
“In animal model studies, we know that if we take this gene away at any point in the life cycle of a mouse, you get symptoms of Rett; it would mimic a child that has a mutation. When you put it back, the symptoms go away,” Monica Coenraads, Executive Director of the Rett Syndrome Research Trust (RSRT), told FoxNews.com.
This initial research was done in 2007 by researchers at the University of Edinburgh and has been confirmed in other labs since.
RSRT is currently funding over 30 studies and the organization’s goal is to drive development of treatments and cures for Rett and related MECP2 disorders.
In May, AJ posted a video on their Youtube channel and website, Magnolia’s Hope— where he’s documented his daughter’s life since her diagnosis— appealing to the Chan Zuckerberg Initiative for research funding and received a response after 24 hours from Facebook founder Mark Zuckerberg. He and his wife Dr. Priscilla Chan, a pediatrician, founded the Initiative in 2009.
“We started the Chan Zuckerberg Initiative to help kids like Magnolia grow up healthy and reach their potential and one of our goals is to cure, treat or manage all disease by the end of the century,” Zuckerberg wrote in the note. “So tell Magnolia we’re working on it and we’re thinking of her.”
“She’s smart, she’s funny, she understands”
For the past two years, AJ, a filmmaker, has stayed home and Jenny, 42, is now home with their newborn son, Grayden Fox.
“We needed all hands on deck,” he said. “When something happens to your kid, you just gotta do everything you can to make sure everything is OK.”
Maggie attends two hours of occupational therapy, two hours of speech therapy, two hours of physical therapy and one hour of horse therapy— her favorite— every week, as well as 15 minutes of vision therapy daily. The family spends about $1,000 a week on Maggie’s care and therapy sessions and insurance covers some of the costs.
Maggie has poor depth perception, but a visit to a specialist in New York City and the addition of eyeglasses helped and thus improved her trust in her body in space. Even though she is sensitive to touch, she knows her glasses help her and therefore tolerates them, her occupational therapist, Uyen Nguyen, OTD, OTR/L, of Developmental Therapy Alliance, in Encino, California, said.
“They are so smart- very aware of everything,” Nguyen told FoxNews.com. “Think about it like a 6-year-old brain trapped in the body of a 2 year old. It will continue to be like that as she gets older.”
Nguyen focuses on Maggie’s balance in engaging in practical tasks, her fine motor skills, bilateral coordination and postural control.
In addition to her inability to verbally communicate, Maggie can’t learn sign language or use visual cards because her left hand is in constant motion and unable to grasp objects and her right thumb is perpetually pulling across her palm. She uses an Tobii Dynavox I-15+ device— which generates speech through the user's eye gaze— to communicate, and though she’s had full conversations on it, the computer’s reliability is hard to ascertain, when it comes to understanding her feelings and physical symptoms.
“She’s smart, funny, understands. She has tantrums on occasion, gets frustrated, she laughs,” AJ said. “Her expressive abilities are the most problematic and whether or not they’re delayed or just all locked into a body and can’t get it out is really the question.”
While she’s not confined to a wheelchair, as some Rett patients are, she has an abnormal gait and skips most of her day.
“It’s adorable, but I don’t know if that’s ultimately a problem and even that is a little abnormal— she goes twice on her left side and once on the right,” AJ said.
When she plays, it has to be directed with hand-over-hand guidance or she uses her computer to tell her parents what to do, such as putting a green block on top of a stack.
The only quiet time is when she sleeps and her arms and hands finally rest still and her breathing normalizes, AJ said.
Rett patients have weaker immune systems than typical children and after Maggie got sick in April, she struggled with standing, walking, sitting on the swing and gripping— all skills in which she had shown improvement. She’s getting better now, but the shifts made AJ realize they weren’t out of the woods and the disease will continue to progress.
“Apparently this is a common thing, they get sick and a lot of Rett syndrome symptoms show up and get worse and worse. Then some [symptoms] get better and some stay,” he said. “Every day it’s like ‘Hey did you notice this?’”
Research has shown that girls with Rett are cognitively intact which is why the Teslers are trying to enroll Maggie in a typical classroom with a personal aid, but their school district thinks a multidisciplinary orthopedic classroom is best for her. They anticipate having to find an alternative method of education for Kindergarten.
“We need to be nimble”
Coenraads, of the RSRT, knows firsthand the ups and downs of the disorder as her 19-year-old daughter, Chelsea, was diagnosed with Rett when she was 2. Her disease is quite severe and she’s restricted to a wheelchair, suffers seizures and requires a feeding tube. Since Coenraads launched RSRT in 2008, the group has awarded $36 million to research, $9 million of which was awarded in 2015.
“We’re trying to discover a cure for a neurological disorder… something that’s never been done before,” Coenraads, who lives in Trumbull, Connecticut, said. “It’s a challenge.”
Research funded by the RSRT has taken a two-pronged approach: Cure-oriented studies looking at attacking the root cause of the MECP2 gene and treatment-centric work aimed at downstream interventions to improve symptoms.
In the cure-oriented studies, one potential option is traditional gene therapy, which would deliver healthy copies of the MECP2 into the brain to compensate for the mutated gene in a one-time fix. Another treatment strategy is protein replacement, which would be an ongoing treatment for a patient, if they find success. Researchers are also investigating whether a healthy, inactive X chromosome can be turned on to override the faulty X chromosome making mutant MECP2 and therefore making healthy protein.
On the symptom end, researchers are looking into unapproved or in-development drugs for other diseases that may be applicable to improve Rett symptoms. For now, patients can be prescribed approved drugs that are repurposed for Rett, such as baclofen for spacicity, anti-seizure drugs and reflux medications.
“It’s not unusual for kids to be on a cocktail of drugs but still have full-blown Rett, but hopefully they’re improving in some symptoms,” Coenraads said. “We know it won’t be a cure, but maybe we can improve seizures, GI problems, rigidity or spasticity.”
Doing clinical trials for the Rett population is difficult because most patients can’t communicate whether the drugs are helping or harming and many Rett symptoms, such as anxiety, are difficult to measure. RSRT has a project underway to improve clinical trial design to provide a blueprint for Rett clinical trials.
“These are all challenging strategies, but certainly testable to see whether they’re doable,” Coenraads said, adding that RSRT needs a continuous source of revenue to keep the trials going in parallel, which may lead to combination therapy solutions.
“We can’t afford to say we only have X million and only can focus on one project and let everything go,” Coenraads said. “We really need to be nimble and act quickly when the opportunity arises.”
Coenraads shied away from sharing projections of real-world application, to manage expectations of families.
“I’m one of those desperate families that wanted a cure yesterday,” she said. “We want to give parents facts. It’s very difficult to put a timeline on things.”
“When there is cure”
Managing Maggie is a day-to-day experiment that AJ jokes has made them amateur geneticists, as they research and try medications, supplements and diet changes while also constantly noting any changes to share with her doctor. Nguyen stays in close communication with all of Maggie’s therapists to ensure she has holistic care and that they’re all aware of her progress and setbacks.
“We help the parents prioritize,” Nguyen said. “These are just amazing parents, so hardworking, so motivating; they always want to do the best for her. Their family is such an ideal family to work with because they follow-through with everything.”
The Telsers’ drive is a contrast to how girls with Rett were handled two decades ago, AJ said. At that time, parents were told to take their daughters home or put them in a group home, and to just love them because there was nothing to be done.
“There’s still nothing they can do now, but they know that there is a spectrum of Rett Syndrome and [parents] can try to work as hard as they can to get them as healthy as you can,” AJ said.
Maggie isn’t enrolled in any clinical trials, but her parents are trying to get her into one for potentially symptom-improving Trofinetide, which has Orphan Drug designation and is being fast tracked by Food and Drug Administration (FDA) , and one for Sarizotan, which may help respiratory problems.
For now, the family celebrates her achievements and spreads awareness of Rett in Magnolia’s Hope videos— she recently blew a bubble for the first time, smiling broadly as she celebrated. Maggie’s favorite things to do include swimming, jumping on trampolines and swinging and she’s a big fan of Frozen and Minions. Providing her with these opportunities is key, AJ said.
“For us important to give her as typical a life as we can and give her as many typical experience as we can,” he said. “So when there is this cure, she will have had all those experiences of a typical childhood.”