CHOC earns $1 million grant to advance rare disease genome-editing therapy

With an aim of addressing a critical and unmet need in rare disease research, CHOC Children’s will advance rare disease genome editing therapeutics, thanks to a $1 million grant from The Larry and Helen Hoag Foundation.

The funding will help form CHOC Children’s Center for Advancing Rare disease Editing (CARE), allowing researchers to further their work to use genome editing to rapidly generate, characterize and treat preclinical models of rare disorders with known pathogenic mutations.

Genome editing therapy has the potential to permanently correct underlying pathogenic mutations in patients with some rare diseases. This treatment addresses the root cause of the disorder, eliminating the need for more standard therapies like enzyme replacement and stem cell transplantation that often require repeated treatments.

“CHOC is at the forefront of operating at the interface of translational research and clinical care of rare disorders,” said Brent Dethlefs, executive director of the CHOC Children’s Research Institute. “Our ultimate goal is to provide patients with rare diseases with an objective, rigorous assessment of whether genome editing therapy has the potential to advance their current standard of care.”

The work will build upon CHOC’s existing successes in developing preclinical models of rare diseases. For example, CHOC’s lysosomal storage disorders research team has already generated the first preclinical models of Pompe disease – a rare and fatal disorder that affects the heart and muscles – that are suitable for genome editing therapy and exhibit molecular, biochemical and functional analogy to patients with the severe infantile-onset form of the disease.

“Given the success of this project, we have received multiple inquiries from research colleagues seeking to collaborate and patient advocacy groups hoping to generate additional preclinical models of rare disease, but until now, we’ve never had the resources to participate,” CHOC scientist Dr. Jeffrey Huang said. “We believe that CARE has the potential for rapid growth given the intrinsic scalability of genome editing as a strategy to generate preclinical models and develop novel therapeutics.”

The Hoag Foundation funding complements a grant CARE recently received from the CHOC Children’s Foundation’s One Wish Grants awards. The grant awards unrestricted funds to outstanding ideas that drive advancement toward CHOC’s strategic goals.

The mission of The Larry and Helen Hoag Foundation is to educate, empower and create greater opportunity for at-risk children to become independent, productive and contributing members of society; support medical research and technology to enhance the health and well-being of children; and support such other compelling purposes that will enhance the quality of life for residents in Southern California.

Learn more about the CHOC Children’s Research Institute.

How pediatricians can help teens get better sleep

Having a teenager in the home can be, for many families, a reminder that there are simply not enough hours in the day. Between school, athletics, after-school commitments, social events and family commitments, many adolescents today feel like they are running on fumes.

While some families accept low sleep as a fact of life for teens, health agencies such as the American Academy of Pediatrics (AAP) are urging adolescents to prioritize sleep for several reasons.

Why are teenagers so low on sleep, and why is sleep so important to them?

Sleep is a topic CHOC Children’s pediatrician Dr. Kate Williamson encounters daily. She estimates that most of her teenage patients are chronically low on sleep.

Dr. Katherine Williamson, CHOC Children’s pediatrician

She points to two key considerations about adolescent sleep:

  1. Adolescents have a different sleep cycle than all other age groups. Their biological clocks signal them to sleep later at night, which mean they need to wake up later the next morning. An alarm set for 5:45 a.m. can feel like the middle of the night to an adolescent body.
  2. Adolescent sleep deprivation contributes to obesity, depression, increasing rates of suicide and declining academic performance, among many other consequences. At a time when academic pressures could not be higher, it’s a dangerous combo.

Williamson is not alone in viewing poor sleep hygiene as a public health crisis. The AAP points to low sleep as a contributor to physical and mental health problems in teens, calls for later school start times and suggests teens sleep eight to 10 hours per day.

The recently signed Senate Bill 328 will require most middle schools to start at 8 a.m. or later, and high schools at 8:30 a.m. or later, beginning July 2022. But legislation is the first step, Williamson says, in a conversation that needs to include parents, educators, health officials and many others.

How can pediatricians help?

For many families, more sleep can be low on a growing priority list—especially when barriers like parent work schedules or differences in socioeconomic status can make changing the routine feel impossible.

This is where pediatricians can step in to help families understand that sleep needs to be the priority for their teens.

Here are some steps pediatricians can take to help teens adopt better sleeping habits:

  1. Start the conversation. Make a point to ask adolescent patients about their sleeping habits and discuss how they could improve.
  2. Talk to patients and parents about the research, including possible consequences of chronic sleep deprivation.
  3. Point out any symptoms you can spot already, such as stress, moodiness or depression.
  4. Urge families to adopt a new sleep routine, and point out that the benefits will outweigh the logistical challenges.
  5. Encourage parents to talk about sleep hygiene with school officials and their workplace/s. Healthier adolescent sleep requires collaboration both within the family and among the wider community.

“Sleep should be addressed by all pediatricians to all teenagers,” Williamson says. “We need to assure families that there is more that goes into this conversation than a new law. It’s about widespread mental health among California’s youth.”

Read more about kids and sleep on

In the Spotlight: Dr. Tammam Beydoun

CHOC Children’s welcomed Dr. Tammam Beydoun to the radiology department in October 2019. Tasked with kicking off CHOC’s Interventional Radiology program, his passion is to use minimally invasive procedures for blood vessel and lymphatic issues. We chatted with him about returning to his hometown of Southern Calif. and his time with CHOC so far.

Dr. Tammam Beydoun, CHOC Children’s interventional radiologist

Where did you receive your education and training?

I did my undergraduate degree at University of California, Irvine, then attended medical school at Touro University California College of Osteopathic Medicine. My radiology residency was at Michigan State University, and my pediatric diagnostic and interventional radiology residency was at Phoenix Children’s. Then, I completed my vascular interventional radiology fellowship at the University of Cincinnati.

What is your role at CHOC?

I was hired to build the new Interventional Radiology (IR) program at CHOC, which is now the only pediatric IR service in the county. IR uses imaging guidance to deliver minimally invasive, targeted treatments across the body. Building on a foundational knowledge of medical imaging, interventional radiologists can navigate the body using imaging to access, diagnose and treat nearly every part of the body, often with just the puncture of a needle. In the past, this used to require open surgical procedures, but now IRs can directly access a target through the skin without a scalpel; they can use the body’s innate transport systems (blood vessels, lymphatics, intestines, etc.) to reach nearly any target.

It’s a satisfying niche that can impact both children and adults. It’s rewarding to work with a large, multidisciplinary team alongside plastic surgery, hematology/oncology, dermatology, general surgery, otolaryngology and other specialties.

Do you have any special clinical interests?

I’m especially interested in biliary (bile duct) and vascular malformations. Abnormal blood vessels and lymphatics can be painful and can lead to a risk for infection and other complications. But using IR, these cases can be treated mostly with minimally invasive needle pokes.

What are some new programs or developments within your specialty?

The IR program itself is new to the county and brings important services to the children at CHOC. We can do a lot of procedures here to help reduce pain, recovery time, length of stay and cost for families. We hope to bring that to an outpatient setting in the future. We’re also working on building a dedicated space for IR, which will continue to supply the team with the most advanced equipment.

What would you most like providers in the community to know about your team at CHOC?

Most people don’t know that IR can affect almost every specialty, such as gastrointestinal, OBGYN, nephrology and many others. It’s a field that can touch almost every part of the body, and there can be a minimally invasive solution for almost every problem – even persistent nosebleeds.

Why did you decide to become a doctor?

If I had to choose a moment when I knew it was for me, I’d pick the Hoag Clinical Care Extender program in 2001. I would see physicians come into people’s lives and change them instantly. As a physician, you can quickly earn a patient’s trust and, with that, really change the course of their life for better. As a person who likes to take responsibility and initiative, I knew I wanted to do that for others. Even if I can’t help them myself, I wanted to be someone who could find them the care they need. It’s a privilege—a heavy privilege—and I don’t take that lightly.

What inspired you to work at CHOC?

It has been my goal to be at CHOC since 2012. I decided in residency that it was my goal to bring IR to SoCal and to CHOC. It’s taken a lot of time and effort, but it happened! This is my hometown, so it’s good to be home and to deliver care where I want to be. CHOC really is the place to go. It’s already a destination for very special care that’s not given anywhere else, and it just keeps improving. The trajectory is steep; CHOC is going places.

What drew you to interventional radiology?

I was drawn to IR because it’s kind of like being MacGyver—a lot of creative troubleshooting. In IR, no two cases are the same. You have a specific set of tools and can use them in any combination to do what you need to do, and you can modify it for any body part and almost any disease. You can go through the groin to work on the nose. You can work with glue, coils or stents. You can see through people with X-rays or CT scans. Each patient requires a novel approach, so I might have to come up with a different way to do something. That’s really fascinating to me.

If you weren’t a physician, what would you be and why?

An engineer. I love solving problems, troubleshooting and anything related to computers, servers or electrical equipment. I’m always taking things apart and rebuilding them.

And a racecar driver, but that dream might be past me now.

What are some of your outside hobbies?

I used to do a lot of outdoor rock climbing, which I’ve pared back on and now do safely indoors. I also love anything automotive, as well as snowboarding.

What have you learned from your patients?

Gratitude and patience. I can’t imagine what some patients go through. Even for the relatively short moment I’m involved in their lives, it can seem like it would be overwhelming. But they do it with patience and gratitude.

Learn more about interventional radiology at CHOC Children’s.

CHOC Physicians, complete the Physician Engagement Survey, receive a messenger bag

The CHOC Children’s 2020 Physician Engagement Survey will be held Feb. 10-28, 2020. CHOC physicians, don’t miss this valuable opportunity to provide your candid feedback, which will allow CHOC to further improve our programs and services to better meet your and your patients’ needs. 

As a token of gratitude, all participants who complete the survey will receive a CHOC messenger bag and will be entered in a raffle for the chance to win a gift card to: The Resort at Pelican Hill, The Ritz-Carlton, Mastro’s Restaurants or Water Grill South Coast Plaza Restaurant. Winners will be drawn each week. Complete the survey early to increase your chances of winning.

Please look for an email on Feb. 10 with your personal link to the survey from Press Ganey, who is conducting the survey on behalf of CHOC. The survey is available on your desktop or smart phone.

If you have any questions, please contact CHOC Business Development: Leslie Castelo at (714) 509-4329,, or Catalina Lawrenz at (714) 509-4363 or

CHOC joins drug trial for rare disease that devastates families

Like most physicians, Dr. Raymond Wang got into medicine because he wanted to help. He wanted to be able to tell patients and their families that he could fix whatever was wrong with them.

When it comes to the disease Dr. Wang dedicated his career to studying, however, he can’t offer such assurances. Hopefully that day is coming.

Dr. Wang and his team at CHOC Children’s are participating in a clinical trial of a drug intended to treat a rare pediatric disease called MPS IIIA. It’s a type of Mucopolysaccharidosis, or MPS, a genetic condition that causes physical abnormalities in young children and causes them to lose their neurological development.

Also called Sanfilippo syndrome, its early symptoms can mirror those of autism, but unlike autism, the patients don’t improve, instead gradually deteriorating until memories and even basic abilities are lost. Most Sanfilippo patients don’t survive to adulthood.

There is currently no cure.

“When we go into medicine, we come in thinking, ‘All right, I’m going to help my patients. I’m going to make them better,’ ” says Dr. Wang, a clinical geneticist and biochemical genetics specialist at CHOC Children’s for the past 12 years. “When you are faced with the prospect that you can’t help, or at least in the sense that you can’t make these kids better and cure them, that doesn’t sit well with me.”

Dr. Raymond Wang, CHOC Children’s clinical geneticist and biochemical genetics specialist

Phases II and III of the trial are being conducted by Lysogene, the French company that developed the experimental treatment. CHOC Children’s is one of four U.S. hospitals taking part; there are three such sites in Europe: in France, Germany, and the Netherlands. Lysogene is still enrolling patients and is seeking a total of 20.

Those patients are hard to find. In his decade of researching MPS and seeing patients, Dr. Wang estimates he’s only diagnosed 10 cases. Two of those children were siblings, and tragically both died of the disease. But Dr. Wang has enrolled one patient in the new trial.

Lysogene sought out Dr. Wang  for the trial because of his expertise in researching and diagnosing the various MPS types. If the Lysogene drug is eventually approved by the FDA, CHOC should become the first facility on the West Coast to be able to both diagnose the disease and administer the drug, which is surgically inserted into brain tissue.

It won’t be apparent until a checkup about six months after the procedure whether the drug is working.

“We are hoping to prevent regression at the least, or allow for developmental progression,” Dr. Wang said.

There have been seven different types of MPS identified: I, II, III, IV, VI, VII and IX, not counting the subtypes within them. The subtype MPS IIIA, Sanfilippo, strikes about one in every 100,000 children.

MPS is an inherited disease. All the types are collectively known as “lysosomal storage diseases.” Lysosomes are compartments in cells that break down molecules and remove waste products.

Normally, different enzymes in the lysosomes break down complex sugars called glycosaminoglycans, also known as mucopolysaccharides. In MPS, glycosaminoglycans are not broken down because of a deficiency in one of those lysosomal enzymes. As a result, the glycosaminoglycans accumulate in the cells and cause tissue damage.

Physical symptoms can include thickening of the lips and skin, enlarged liver and spleen, hernias, recurring ear infections, joint pain and stiffness, and shortness of stature. With Sanfilippo, which attacks brain cells, cognitive impairment could include delayed speech. Since by itself speech delay isn’t uncommon in children, Sanfilippo’s initial symptoms only add to the confusion for families.

In the first two to three years of a patient’s life, “there might not be any symptoms,” said Dr. Wang, director of CHOC’s Foundation of Caring Lysosomal Storage Disorder Program . “Nobody ever thinks ‘my kid has Sanfilippo,’ and few doctors think about it. But it starts to be around 3, 4, 5, when hyperactivity starts, and there are questions of autism, and usually what happens is a physician recognizes that kids with Sanfilippo look a little different.”

A treatment that has shown success for some kinds of MPS is enzyme-replacement therapy: delivering synthetic working enzyme using an intravenous solution. It can reduce the effect of symptoms and improve quality of life. But the treatment only works if the disease is not located in the brain; unfortunately, the life-threatening symptoms of Sanflippo are caused by effects of the disease in the nervous system.

Inside the brains of children with Sanfilippo syndrome, a waste product called heparan sulfate builds up, causing nerve damage and, over time, the death of nerve cells. The Lysogene drug includes a package called a “vector.” It contains genetic instructions that enable treated nerve cells to make the missing enzyme, called sulfo-hydrolase, which clears out the waste product.

“Short-term, you can measure things like, is the body producing sulfo-hydrolase enzyme; is there a reduction in heparan sulfate?” Dr. Wang says. “But the more important thing is, is this actually helping these children? What parents really care about is, is it helping their child’s neurologic function. Is my child not regressing? Is my child maybe even gaining developmental milestones back?”

Dr. Wang acknowledges that, as a younger doctor, he was fascinated by the diagnostic side, the “sleuthing” part of identifying patients with, and researching, MPS. But over time, after accompanying many MPS patients and their families along difficult and tragic journeys, he knows his motivations now have a higher purpose, beyond intellectual stimulation.

He reflects that his involvement in clinical trials for children with neurodegenerative conditions such as the Lysogene study is “a way for me personally to channel my feelings of helplessness when we diagnose someone with a supposedly incurable condition.”

“I know how painful it is for these families,” Dr. Wang says. “If I can give them the possibility of hope, then that’s what makes waking up each morning and heading to work worthwhile.”

Learn more about referring to CHOC’s metabolic disorders specialists.