Searching for hope while living with a rare disease

Rocio Macias was driving when her 4-year-old daughter, Isabella, coughed from the backseat.

“Are you OK?” Rocio asked.

“I’m OK,” Isabella answered with a giggle.

While likely mundane for many parents, this exchange is the stuff dreams are made of for Rocio, the mother of a child with a devastating rare disease.

“She’s doing well – she’s trying to talk a lot more,” Rocio says. “I see things physically too – she doesn’t fall as much as she used to. She doesn’t bang her head much anymore.”

Isabella is in the early stages of a clinical trial at CHOC Children’s that will evaluate a drug intended to treat a rare pediatric disease called MPS IIIA. The condition is 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. Unlike autism, though, the patients don’t improve. Instead, they gradually deteriorate until memories and even basic abilities are lost. Most Sanfilippo patients don’t survive to adulthood.

“You ask, ‘What is that? What can I do? What can be done?’ For this one, there’s no cure. And you just cry,” Rocio says.

But Rocio found a glimmer of hope in the trial, Dr. Cristel Chapel-Crespo, Isabella’s CHOC metabolic specialist at CHOC, and Dr. Raymond Wang, also a CHOC metabolic specialist who is the director of CHOC’s Foundation of Caring Lysosomal Storage Disorder Program.

Joining the clinical trial

Phases II and III of the trial are being conducted by Lysogene, the French company that developed the experimental treatment. CHOC is one of four U.S. hospitals taking part, with several other sites in Europe.

Those patients are hard to find. In his decade of researching MPS and seeing patients, Dr. Wang estimates he’s only diagnosed 10 cases. However, given the deep heartbreak that Sanfilippo syndrome can cause with parents of affected children, Dr. Wang sought out Lysogene as a partner to provide families with access to clinical trials – and hope.

Lysogene, in turn, 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 U.S. Food & Drug Administration, 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.

For Isabella, participating in the study meant traveling to New York, where she received the medication in June 2019.

Following a seven-hour surgery, Isabella spent a night in the hospital’s intensive care unit. The family stayed in New York for another week of tests, and then returned home.

After one more check-up in New York, the family began follow-up treatment in December much closer to home at CHOC with Drs. Chapel-Crespo and Wang, and will continue to do so every three months for five years.

“She has no after-effects at all from the surgery, is happy and doing well,” Dr. Wang says, adding that Isabella will continue to take anti-rejection medication throughout the first year of the study.

“We are hoping to prevent regression at the least, and ideally see developmental progression,” he says.

The effects of Sanfilippo

MPS IIIA, or Sanfilippo, is a subtype of MPS that affects about one in every 100,000 children. Overall, seven different types of MPS have identified: I, II, III, IV, VI, VII and IX, not counting the subtypes within them.

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 a 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,” Dr. Wang says. “Nobody ever thinks ‘My kid has Sanfilippo,’ and few doctors think about it. But it starts to be around age 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 mother’s instinct

Rocio began noticing some symptoms in Isabella when the toddler was about 2. Rocio thought she could explain Isabella’s unsteady walk and slow speech, but that her daughter wouldn’t outstretch her arms to catch herself when she stumbled was especially alarming.

“As a parent, you start looking around at the other kids in the class and think, ‘Is there where the other kids are too?’” Rocio said. “I never looked at it like something was wrong – I just thought she was delayed.”

As Rocio pursued speech and physical therapy for Isabella, CHOC otolaryngologist Dr. Kevin Huoh was separately evaluating Isabella for her snoring. After observing some of Isabella’s physical features, Dr. Huoh quickly referred the family to CHOC’s genetics team. Subsequent genetic testing revealed her condition.

Learning the diagnosis was devastating for Rocio. After taking the call in an empty office at work and bursting into tears, she needed to leave early for the day, she recalls. With her husband in an all-day training, Rocio was forced to deliver the news by text message.

The medication’s hope

The news was made especially frightening when the couple learned there was no treatment for Sanfilippo.

While enzyme-replacement therapy has successfully treated some types of MPS, it only works if the disease is not located in the brain. Unfortunately, the life-threatening symptoms of Sanfilippo 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 relevant question is, is the investigational treatment actually helping these children? What parents really care about is, Is it helping my child’s neurologic function? Is my child not regressing? Is my child progressing normally? If there were lost developmental milestones, is my child maybe even gaining them back?”

Moving forward

While Rocio has already anecdotally noticed some improvements in Isabella, time will tell whether the drug is truly effective. In the meantime, the family has found additional support through the rare disease community. They attended a local event for families impacted by MPS. Isabella was the only child with MPS IIIA.

They’ve also found some solace online, though Rocio participates only in measured doses.

“It’s hard. Sometimes I tell my husband I don’t want to follow the groups anymore,” she says. “People post when someone passes away – and it seems like that happens every day. The other day it was an 8-year-old, and you think, ’Shoot, Isabella is 4,’ and that’s heartbreaking. But then someone posts about a 27-year-old and that gives me hope.”

Rocio also continues to take her family’s journey one day at time – after all, she’s adjusting a new reality of parenting a medically complex 4-year-old as well as a 2-year-old daughter, who is not a carrier for Sanfilippo.

“I went from having a life to having a totally different life,” she says.

Learn more about research at CHOC

Related posts:

Three gifts support mental health, research and neonatal care

CHOC Children’s is so grateful to recently have received three very generous gifts that will help CHOC continue to care for more than 185,000 babies, kids and teens each year. CHOC believes that all children deserve a chance at a happy, healthy childhood.

Transformational gift to benefit the pediatric mental health system of care

CHOC received a transformational gift from the Cherese Mari Laulhere Foundation to enhance and expand its pediatric mental health system of care. The announcement comes on the heels of the Conditions of Children in Orange County report, which highlights alarming increase in the number of children hospitalized in the county for mental illness.

The gift from the Cherese Mari Laulhere Foundation will:

  • Endow CHOC’s mental health inpatient center. Opened in April 2018 for children ages 3 to 17, the center is the only inpatient facility in Orange County that offers specialized programs for kids younger than 12. The center will now be named the Cherese Mari Laulhere Mental Health Inpatient Cente
  • Establish the Cherese Mari Laulhere Young Child Clinic for children ages 3 to 18 who are experiencing behavioral and emotional challenges, mental health issues and school readiness challenges.
  • Expand CHOC’s Intensive Outpatient Program, a mental health treatment program for high schoolers with moderate to severe symptoms of anxiety, depression or other symptoms related to mental health conditions. The program will be expanded to middle school-aged children.
  • Advance trauma-informed care, including providing tools to pediatricians to help in identifying adverse childhood experiences, and connecting patients and families with resources.
cherese
Cherese Mari Laulhere

“Our donations are gifts from our daughter, who brought so much light and love into this world. As someone who advocated for the underserved, Cherese would be very proud of her role in supporting CHOC’s mental health efforts and helping change the trajectory of thousands of young lives,” says Cherese’s parents, Chris and Larry.

Learn more about this gift to CHOC Children’s.

$8 million to advance research for rare disorder

An $8 million gift from the Foundation of Caring will help CHOC advance research for a rare lysosomal storage disease, ultimately leading to an improved understanding and more effective treatments.

The gift will support CHOC researchers working to develop next-generation therapies for Pompe disease, a lysosomal storage disease wherein glycogen builds up in the body’s cells and causes life-threatening heart failure and muscle weakness in affected babies. In honor of the gift, the program will be named the Foundation of Caring Lysosomal Storage Disorder Program at CHOC Children’s.

The work of Dr. Raymond Wang, a CHOC metabolic disorders specialist and director of the Foundation of Caring Lysosomal Storage Disorder Program, drew the attention of the Foundation of Caring several years ago when Dr. Wang began treating the great-granddaughter of the Foundation’s founder after she was diagnosed with Pompe disease.

raymond-wang-md
Dr. Raymond Wang, a CHOC metabolic disorders specialist and director of the Foundation of Caring Lysosomal Storage Disorder Program

With previous support from the Foundation of Caring, Dr. Wang and his team have already made significant strides in its study of Pompe disease, having built a growing research team that’s used CRISPR/Cas9 technology to edit the genome to create animal models of Pompe disease. The Foundation of Caring’s gift will allow Dr. Wang and his team to expand upon this work and use CRISPR to cure Pompe disease and lysosomal storage disorders.

“We are so pleased to support the important work of Dr. Wang and his team at CHOC to help find better treatment or, even better, a cure for Pompe disease for patients affected by the condition worldwide,” says the Foundation of Caring Board of Directors.

Learn more about this gift to CHOC Children’s.

$2 million to CHOC’s neonatal intensive care unit

Newborn babies requiring critical care have gained a big ally in the William, Jeff and Jennifer Gross Foundation. A recent $2 million gift to the neonatal intensive care unit (NICU) on CHOC’s main campus in Orange rounds the Foundation’s support of CHOC’s neonatal services to $7 million in the past year.

choc nicu

Many hospitals offer intensive care units but only a select few are rated by the American Academy of Pediatrics as Level 4 – the highest rating available – and even fewer are ranked among the best in the nation, according to U.S. News & World Report. CHOC’s program features three NICUs, a team of board-certified neonatologists and special units for the smallest preemies, infants who need complex surgery, and babies who have neurological and cardiac concerns.

“CHOC’s neonatal services are unlike anything else offered on the West Coast, providing the highest levels of care and tremendous hope to families in the region. We are honored to continue our commitment to CHOC and the care of newborn babies,” says Jeff Gross.

Learn more about this gift to CHOC Children’s.

Related posts:

CHOC at Forefront of Treating Rare Genetic Condition

Just two weeks after losing their 6-year-old son to a rare and fatal genetic brain condition, Bekah and Danny Bowman began the first of many cross-country trips with their 3-year-old son in hopes that a new treatment would spare the younger boy from the same fate as his brother.

Ely was diagnosed with CLN2 disease, also known as late infantile Batten disease, shortly after his older brother, Titus, was found to have the same condition following nearly two years of symptoms. Batten disease typically begins with language delays and seizures before age 3, and rapidly progresses to dementia, blindness, loss of the ability to walk and talk, and death in childhood.

Beginning to show a speech delay, Ely would travel with his parents from Orange County to Columbus, Ohio, every 10 days to participate in a clinical trial wherein he would receive an infusion of a medicine that researchers believed would slow the disease’s progression.

But now, the Bowmans need only to drive a few miles to CHOC Children’s Hospital for this critical treatment. CHOC has become one of the first hospitals in the United States to offer Brineura, which the U.S. Food and Drug Administration approved in April as the first and only treatment for Batten disease.

ely-bowman-choc-batten-disease
Ely at CHOC for Batten disease treatment.

Over a three-year period, patients like Ely who were treated during the clinical trials showed no progression of the disease, which was radically different from the disorder’s natural course. The medication improves quality of life and buys patients critical time as researchers continue to search for a cure.

CHOC has been fast tracked to provide this novel new therapy commercially, which requires making a reservoir in the brain to give an infusion every two weeks.

Brineura’s availability at CHOC is also a game changer for Maya James.

Diagnosed with an atypical form of Batten disease about four years ago, the 14-year-old had also been traveling regularly to Ohio to participate in the clinical trial.

While the medicine has been shown to slow the progression of Batten’s devastating consequences, Suzette, Maya’s mother, says the treatments have helped her daughter improve her balance and walking. Maya continues to ride a bicycle and rock climb.

The treatment has given the James family hope.

“We’re so thankful to have this opportunity,” Suzette says. “Before, we had nothing. We only had, ‘Your child is going to die and we can’t tell you when. And she’s going to lose every function she has and we can’t tell you when.’ It’s truly groundbreaking what CHOC is bringing for patients with neurological conditions. This is an opportunity for people with other similar diseases to have hope.”

Maggie Morales was preparing to bring her daughter Mia to Ohio for treatment when she got a call from CHOC about Brineura’s availability.

Now, Mia, 5, has completed more than six infusions of the medicine, and her family has found a sliver of light following a devastating diagnosis last year.

batten-disease-treatment-choc
Mia receiving treatment for Batten disease at CHOC.

“It’s amazing that there’s treatment because when we first got the diagnosis, there was nothing to do but take your child home and wait for it to happen,” Maggie says. “Hopefully along the way, a cure comes along. “

Bringing Brineura to CHOC is the product of three years of work by Dr. Raymond Wang, a metabolic specialist who treats Ely, Maya and Mia.

Dr. Wang works closely with neurosurgeon Dr. Joffre Olaya to administer the medicine. Each patient has an Ommaya reservoir implanted under their scalp, which allows the medicine to be infused directly into their brains.

In a sterile procedure every 14 days, Dr. Olaya and a team of highly trained nurses insert a needle into the reservoir to administer the medication. The infusion lasts four hours, and after four hours of observation, the patients can go home.

“This is huge,” Dr. Wang says. “You’re taking a progressive and fatal disease and stopping it. Having seen how heartbreaking it is for families to see the child they know get slowly robbed from them, the fact that we can offer these families hope, is tremendous. Something like this is the very reason I went into medicine and specialized in metabolic disorders: to provide hope to families affected by rare disorders such as late infantile Batten disease.”

As he receives his infusion, Ely wears medical scrubs with “Dr. Ely” embroidered across the chest and watches videos on an iPad. Flashing across the tablet’s screen are home movies of Ely as a toddler playing with his late older brother.

The Bowman family will never get back those days, but this life-saving treatment at CHOC is an opportunity to halt a disease that has ravaged their family.

“For Ely to be home and have consistency and we can still have some fun is wonderful,” Bekah says. “We can see him thriving.”

Learn more about metabolic disorders treatment at CHOC

Meet other CHOC patients:

  • Augustina’s heroic battle with COVID-19
    When Augustina, then age 13, visited her doctor in early June because she wasn’t feeling well, she had no idea she’d be rushed to CHOC Children’s Hospital and spend the ...
  • CHOC patients meet with legislators for advocacy week
    CHOC Children’s patients Zachary and Jennifer, along with their families, recently participated in virtual meetings with legislators as part of ongoing advocacy efforts. “Each family met virtually with their members of ...
  • A magical emergency department visit
    When 3-year-old Vinny and his mom Nikki visited CHOC Children’s for the first time, they didn’t expect a calming experience thanks to a magic show, or that staff would go above and beyond to ...

What We’re Thankful for This Year: 2016

In celebration of Thanksgiving, members of the CHOC Children’s family express what they’re most grateful for this year.

thanksgiving at chocMary Green 

Registered nurse in the Hyundai Cancer Institute at CHOC Children’s

“I could list 100 reasons why I am thankful for CHOC. I’m thankful to work at a place with such visible growth: in the number of available treatments, in the percentage of children that are surviving cancer, in relationships between patients, family members and staff; and growth visible in children as they begin to believe how strong they truly are. Even more so, I am thankful that CHOC is passionate about celebrating growth and takes pride in celebrating all of the little things.”

thanksgiving at chocDr. Joanne Starr

Medical director, cardiothoracic surgery

“I’m grateful to be part of an innovative pediatric hospital and for CHOC’s commitment to providing patients and families with access to the best neonatal and open-heart surgery in Orange County.”

thanksgiving at chocDana Sperling

Social worker, NICU

“I am thankful for two amazing teams I am privileged to be a part of:  the social services team and the Neonatal Intensive  Care Unit (NICU) team.  The compassion and dedication of both teams makes me proud to work along side them day after day, delivering outstanding care to patients and families.”

 

thanksgiving at chocDr. Kenneth Grant

Chair of gastroenterology 

“I am thankful to be working for an organization that creates an environment where our patients become our family. I am also grateful that CHOC Children’s has the foresight to invest in the innovative ideas we have to improve the health care we provide. ”

thanksgiving at chocDr. David Gibbs

Medical director of trauma services

“I am thankful for the trust of our patients and families. With the strong support of the hospital and the community, our Level 2 Trauma Center is proud to care for children in Orange County.”

thanksgiving at chocJoani Stocker

Volunteer

“I am so thankful for the opportunity to bring smiles and laughter to our patients through Turtle Talk and the playrooms. Laughter is medicine to the bones, and I am humbled to be a part of the healing. My cup is overflowing with joy when I see a patient giggle and play.”

thanksgiving at chocDr. Daniel Mackey

CHOC Children’s pediatrician

“I am thankful for the opportunity to be partnered with an excellent children’s hospital. I am also thankful for the pleasure of working with other positive people who provide outstanding care to the children of Orange County. Together we work to improve the care and services we deliver to our most important resource…our children.”

thanksgiving at chocDr. Gary Goodman

Medical director of the Pediatric Intensive Care Unit, CHOC Children’s at Mission Hospital

I am most grateful to the people behind the scenes at the hospital that do all the invisible jobs that are so important to keep CHOC Children’s running: the housekeepers, lab and x-ray technologists, bio-medical engineers, pharmacy technicians, scrub technicians, security guards and maintenance staff that work tirelessly, 24-hours a day.”

thanksgiving at choc

Dr. Raymond Wang

Metabolic disorders specialist

“I am thankful that CHOC cares for families and children with rare disorders by supporting clinical trials and translational research, and the staff who care for these families, to find treatments and cures for their conditions.”

thanksgiving at chocEric Mammen

Lead music therapist

“I am grateful that I get to witness the transformative powers of music with amazing patients and families everyday here at CHOC. So very grateful for the generous donors that continue to support our growing music therapy program. Without them we would not be able to impact the families and help them face incredible challenges with courage, smiles, and a song. Super grateful to be apart of writing a powerful song with a patient in response to his medical diagnosis- “To Life Live To The Fullest!” Happy Thanksgiving and I hope you get to spend some extra time with your loved ones around you.”

Matt Gerlachwhat choc is thankful for

Executive vice president and chief operating officer

“At this time of Thanksgiving, I am thankful for CHOC Children’s and the wonderful service we are privileged to provide for the communities we serve. I am thankful for the dedication and commitment of our physicians, associates and volunteers, who give the very best they have to give— their knowledge, skills, abilities, care and compassion— to make CHOC’s mission to nurture, advance and protect the health and well-being of children a reality for so many in need, every day. I am also thankful for those that stand behind our physicians, associates and volunteers— their loved ones, who support our CHOC Children’s team to be the best that they can be, both at work and at home. I wish all of our CHOC Children’s family a happy and healthy Thanksgiving.”

Related posts:

  • An innovative internship approach during COVID-19
    A year ago, Jenae Vancura joined an elite group of college and high school students for a unique and innovative summer internship program at CHOC Children’s. The interns shadowed physicians, ...
  • How being an athlete prepared me to be a nurse
    By Elyse Shelger, registered nurse at CHOC Children’s In my life before nursing, I was a soccer player. I started playing the game when I was 4 years old. It shaped ...
  • One nurse’s thank you letter to a former patient
    By Amanda Paragas, registered nurse, CHOC Children’s cardiovascular intensive care unit The CHOC Children’s RN Residency Program is a 17-week program that is specifically customized to meet the requirements of the ...