2024 Breakthrough Makers
Making music, mending hearts
A jubilant sound was heard above the array of beeping monitors in one CHOP patient's Cardiac Intensive Care Unit (CICU) room this summer. The toddler — who had endured many difficult medical experiences throughout his extended time in the hospital — was awaiting a heart transplant.
The patient had recently become interactive after recovering from a significant medical procedure. Lydia Westle, MMT, MT-BC, a music therapy clinical expert in CHOP's Child Life, Creative Arts Therapy & Education Department, took advantage of the opportunity to play guitar and sing the child's requested song: "Head, Shoulders, Knees and Toes." The singing provided developmentally appropriate stimulation for the patient, enhancing his coping ability and helping to override the sounds produced by the myriad monitors in the room.
When the patient's nurse, Ryan Brown, RN, witnessed how positively the patient was responding to the well-loved song, he immediately joined in and started singing with Lydia, simultaneously doing the motions in an exaggerated, silly manner. Soon George Samuel, RN, walked by the open door and, upon seeing the interaction unfolding, began singing and dancing with the others.
"The patient's face immediately lit up — he started smiling and laughing and repeatedly pointed at Ryan," says Lydia. "I invited the patient to 'conduct the band' while the two nurses danced and sang to his cues. This gave the patient a wonderful opportunity to have control, make choices and experience a sense of leadership."
To the patient's delight, three other Nursing and Clinical Care Services team members joined in on the experience: Steph Braun, CPNP; nurse resident David Akinwande; and Reece Young, RN. None of the singing and dancing participants had ever met Lydia, but it didn't matter. They responded intuitively to what was happening in the room and collaborated to create a cherished moment for this patient and his mother. The patient beamed from ear to ear for the first time in a long while.
"It was so powerful and beautiful to see the joy that this experience brought the patient, as well as his mother, who witnessed it," says Lydia. "For a moment, they were able to experience such a typical parent/child interaction — filled with love and laughter — in the midst of a really challenging, prolonged hospital admission."
"The joy in the room was contagious. In the midst of everything happening in the world, this helped bring us [the CICU team] back to our 'why' regarding this work. We are all so grateful and humbled to be working at CHOP with such inspiring patients and families as part of an amazing interdisciplinary team."
Celebrating environmental services
From 2019 to 2021, CHOP's Environmental Services team participation in the annual employee engagement survey had dwindled. The group's senior manager, Nicole Seon, heard repeated comments from team members saying they weren't confident the survey was confidential. In addition, they weren't convinced that leadership would act upon the survey results even if they did take it. There was a feeling of "What's the point?"
Even after concerted efforts to encourage survey participation and repeated assurance that the survey was completely anonymous, the team's participation numbers continued to decrease. It was time to do something different.
"In 2019 and 2020, we looked at our engagement survey results as a leadership team and asked ourselves, 'What can we focus on that's going to really drive improvement?'" Nicole recalled.
Nicole and other Environmental Services leaders decided to focus on five or six concerns based on feedback from the 2020 survey. When the 2021 Engagement Survey results were released, change hadn't happened as the group had hoped it would, prompting Environmental Services leaders to believe that they had focused on addressing too many concerns at once. They went back to the drawing board.
"We realized it is critical to use CHOP's manager engagement toolkit," Nicole said. "It guided us to focus on one or two initiatives to help improve engagement, not five or six as we had done in the past."
Moving forward, this leadership team chose three areas of concern to focus on because they felt that each was very important. The themes focused on team members craving more respect and feeling they weren't recognized enough for their hard work, not just within their department, but outside the department, too. They also felt as though decisions were made that affected their job without ever asking them for input or feedback.
"We did focus groups on each unit, asking team members what they needed to improve their work experience, and what we found is that really small things make a big difference," Nicole recalled. "The team talked about wanting their efforts to be recognized by their clinical partners."
It was identified that some units had welcome boards with profile pictures of everyone on the team, with the exception of Environmental Services team members. Sometimes when there was a celebration of an accomplishment on the unit, they weren't included. These types of incidents left the Environmental Services team feeling as though they weren't part of the overall unit team.
Environmental Services leaders began to collaborate with their units' clinical partners, sharing these concerns. The response was powerful: Environmental Services team members were invited to unit celebrations, and birthday boards were created so everyone in the unit knew whose birthday was coming up. In addition, CHOP's Bravo Recognition Program became mandatory for every Environmental Services teammate, with each having to recognize at least three co-workers who went above and beyond while performing their daily tasks.
The action taken by Environmental Service leaders was noticed by team members, who could see that their feedback had been heard and action had been taken in response to it. Participation in the employee Engagement Survey increased from 37 percent in 2021 to 70 percent in 2022!
"We're headed in the right direction," Nicole said. "Engagement is year-long — it's every day and taking every opportunity to tell your team that what they do matters, that sharing their voices makes us all better. If we take care of our teams, they're going to take care of the patients, the families and each other."
Compassion and collaboration
A patient and his mother arrived at Voorhees Specialty Care and Surgery Center (SCC) in New Jersey for an electrocardiogram (EKG), a non-invasive and routine test to measure heart function. Shortly after arriving, the patient showed signs of distress that increased quickly, causing stress to his mother as well. Rachel Keashen, CPNP, and Voorhees staff took appropriate steps to de-escalate the situation without success. Luckily, several social workers who are not specifically assigned to the Voorhees SCC happened to be onsite that day. Rachel engaged Carissa Fleming, MSW, LSW, Outpatient Oncology Social Worker, and Deja Houser, MSW, LSW, Hematology Social Worker, and briefed them on the current situation.
Upon entering the room where the patient and mother were still showing escalating signs of distress, Deja and Carissa escorted the parent out of the room to give her a moment to self-regulate and call in other familial support. Meanwhile, these social workers returned to the patient and tried multiple techniques, such as breathwork and stress balls, and provided verbal support to try to calm him down. At this time, Alessio Pisano, LPC, ACS, NCC, Licensed Mental Health Clinician, arrived to assist the situation. Together, the team cleared the room to reduce any threat of patient harm while Alessio spoke to the patient, attempting to help normalize his feelings of distress. Meanwhile, Deja returned to the patient’s mother to offer additional support.
After some time, she calmed down and returned to the patient with Deja, Carissa and Alessio. Together, they made it clear to the patient that he was not in trouble for his behavior or for not completing the EKG. The patient pulled on his shoes while staff cleared the hallway so he could exit the building without additional stressors or attention. Rachel rescheduled his test and engaged Rachelle Pollock, LCSW-NJ, LSW-PA, Intake Social Worker for Specialty Care Centers in NJ, to make a plan for his next visit. Rachelle met with Deja and Carissa and also brought in Vikki Kalbacher, LMSW, Social Worker, to collaborate on a comprehensive plan. They also called the patient’s mother to offer community resources and advice for their rescheduled appointment. At the patient’s next appointment, Rachelle was onsite to meet with staff before the appointment and developed a plan for de-escalation if needed. The Voorhees team also made sure the patient's time in the waiting room was limited.
With patient and staff prepared, the entire visit only took 15 minutes without incident. The grateful mother expressed her appreciation for everyone involved.
A questioning attitude, a lifesaving diagnosis
Something seemed off to Sarah Weston, RD, CSP, LDN, after examining a 20-month-old patient and discussing her symptoms with the little girl’s parents at their appointment. The patient was initially seen at CHOP in Nov. 2022 with severe malnutrition due to an inability to get enough nourishment from eating orally. She had been referred to Sarah — a Clinical Dietician III and CHOP employee of 15 years — by her gastroenterologist to evaluate her growth.
After the patient had spent some time on a feeding tube, her gastroenterologist appropriately weaned her off the assisted feedings but — about two weeks prior to her appointment with Sarah — the patient started sleeping more, was walking with an unsteady gait and vomited multiple times each day.
The family felt these symptoms were related to being weaned off the tube feeds and multivitamin about a week before these symptoms presented. But as Sarah continued to ask more questions to get to the bottom of what was happening, she felt concerned that the health issues the child was experiencing were not related to diet.
"The patient's family felt strongly that these symptoms were nutritional in nature since the tube feeds and multivitamin had stopped right before the onset of symptoms," Sarah said. "They were requesting to restart tube feedings and the multivitamin."
Still, the scenario didn't add up for Sarah: the patient's oral intake and weight gain had been excellent — she was no longer malnourished. In addition, the acute onset of symptoms didn't align with malnutrition, and the short duration and intensity of symptoms made Sarah concerned that the child was experiencing a medical problem.
"I assured the parents what I could," said Sarah. "That the unsteady gait, vomiting and lethargy were not nutritional. I disclosed that I was unsure what was wrong, but that these symptoms clustered together bothered me."
After encouraging the parents to reach out to their pediatrician while on their way home from the appointment, Sarah immediately sent a secure message to the child's primary care physician and gastroenterologist outlining her concerns. She carefully documented the reasons she believed this situation was not nutritionally related in the patient's electronic medical record. She wanted to ensure the doctors had the necessary details to make an informed decision.
The family ended up reaching out to the child's gastroenterologist first, who, upon reading Sarah's documentation and intake history, referred the child to her primary care provider and the emergency department (ED). The primary care doctor also referred the child to the ED. That same night, the child was admitted to the ED, where they discovered she had a suprasellar mass on her brain with associated hydrocephalus.
An innovative rescue mission
In 2019, an operating dilemma came to light when CHOP received a citation from the Joint Commission — the nation's oldest and largest standards-setting and accrediting body in health care. The Joint Commission evaluates health care organizations such as CHOP to help them excel in providing safe and effective patient care. The reason for the citation: When asked during the Joint Commission survey how to open a locked patient bathroom if a patient was unable to open the door from the inside, CHOP team members were at a loss.
After the survey, a corrective action plan was put into place to educate team members on the appropriate practice for unlocking bathroom doors, but the plan was not sustainable and varied by location, making standardization of the process impossible. There were many different door handles and lock systems throughout the hospital, with the most prevalent being a coin-type slot in the door handle that is difficult to open from the outside when the lock is activated inside the bathroom. These locks do not open with a key, so previous solutions included using a coin, washer or badge to unlock the door, but these presented other challenges, including choking and MRI safety concerns.
The Safety Quality Specialist (SQS) team began to consult with the Human Factors team during their weekly office hours. From there, a multidisciplinary team was created to assess current processes and develop an improvement plan that would not only satisfy regulatory requirements but, most importantly, improve patient safety. The team consisted of representatives from Nursing, Regulatory, Facilities and Human Factors Engineering.
One of the first ideas the team had was to chan
ge out all impacted bathroom door locks with ones that did not require any tools or coins to unlock them. This was ultimately deemed impractical because of the cost involved. Similarly, several products that were available to purchase were vetoed because of safety concerns involving metal and the MRI machine, as well as patient choking risk.
Ultimately, the team approached the Children's Hospital Additive Manufacturing for Pediatrics Lab (CHAMP) to explore the possibility of a solution that was designed and manufactured in-house and addressed all the safety concerns that had been voiced. The CHAMP lab created prototypes of solutions and collaborated with Human Factors Engineering to conduct user acceptance testing with nursing team members.
The final product, dubbed "Bathroom Rescue," was printed on a special 3D printer in collaboration with UPenn Engineering's AddLab; over 450 of the Bathroom Rescues were fabricated there. Next, a standardized location for the Bathroom Rescue was identified in all patient care areas at CHOP. The device is currently housed at each nursing station and code cart, as well as with Security, Nursing Operations and Facilities. All nursing staff were educated and trained on how to use the device, and policies were created to ensure daily checks for its integrity and availability.
Recently, two patient safety events occurred that highlighted the effectiveness of using the Bathroom Rescue to safely care for patients. In each of these events, the Bathroom Rescue was able to be used successfully because of thorough staff education, training and muscle memory. Staff reacted quickly to provide safe, emergent care to the patients involved.
The Bathroom Rescue project exemplifies CHOP's pursuit of excellence and continual advancement beyond the ordinary to create innovative ways to deliver the highest level of care and safety to patients and their families. The Bathroom Rescue team has even reached out to Technology Transfer to explore potential intellectual property opportunities that would enable Bathroom Rescue to be shared beyond the walls of CHOP.
Hands-on health: A fresh take on fruit
Abbe Stern, Food Pharmacy Manager and Food Justice Program Coordinator in the Center for Healthy Equity here at CHOP, recently visited Alain Locke School in West Philadelphia and created a unique food distribution opportunity.
Abbe is currently enrolled in a master’s program in Healthcare Innovation at Penn. She learned from a colleague, Jared Beck, Alain Locke’s Community Schools Coordinator, that the students at his school receive lunches from the School District of Philadelphia, but many students end up throwing away the food because it is not appetizing. Thanks to her connection with Jared, Abbe was able to observe a lunch period at the school to learn more for her class assignment about policy changes around school meals.
During her observation, she was stopped by kindergarten teacher, Dara Messing. The two got to talking, and Dara mentioned that she was teaching her kindergarteners about fruit. After hearing about Abbe’s role at CHOP, Dara asked if Abbe could help her get some fresh fruit for the students to connect with the lesson. They did some brainstorming and decided to help the kindergarteners host a fruit stand!
Abbe purchased $300 worth of fresh fruit with resources from CHOP’s Food Pharmacy Program and prepped fruit cups for the students. Dara set up a “fruit stand” in the school cafeteria, and the kindergarteners made signs and fruit headbands to wear while they handed out the fruit.
“The kids got to talk about each of the fruits and try each one while they made the cups. We really wanted them to be involved,” said Abbe.
With a little help, the kindergarteners served around 250 fruit cups to their fellow students and teachers. Not only did this provide a healthy snack for the students at Alain Locke, but it was also an educational opportunity for the youngest students to learn about and taste test different fruits.
Abbe shared, “The kids had so much fun. They really felt like they were owning the process, and every kid in the school was so happy to have fresh fruit.”
While the systemic issues of food accessibility and school meal policies can’t be solved overnight, initiatives that seem small – like a kindergarten fruit stand – can provide an important introduction to healthy foods for children.
Hearts connected
At CHOP, we do all we can to provide top notch medical care, which includes the emotional well-being of our patients and their families. In May 2023, the oncology unit at Main Hospital admitted a young patient for chemotherapy, requiring him and his mother to stay at CHOP for several days. During his admission, the patient's grandfather, whom the mother described as "his #1 person", was receiving end-of-life care for his own cancer diagnosis next door at the Hospital at the University of Pennsylvania (HUP). Marissa Larose, Charge Nurse, and Lauren Ferguson, Flow Facilitator, started the day pass process just in case it was needed during this patient's stay. Day passes are approved at the discretion of the multidisciplinary care team for each individual patient in the case of a once-in-a-lifetime event. Day passes are rarely granted — only if and when the care team decides it's safe for the patient to leave the hospital.
The next day during rounds, Rachel Most, Clinical Nurse Expert; Hannah Ness, Oncology Charge Nurse; and Sarah Sexton, Clinical Nurse, advocated for this patient to be granted a day pass to visit his grandfather. The request was granted provided that the patient complete his chemotherapy regimen first. This patient's plan not only included receiving intravenous chemotherapy, but also several hours of hydration afterwards to keep his body safe from the effects of chemo.
Shortly after this plan was made, the mother received a call that her father's condition was rapidly deteriorating, and he was specifically asking to see his grandson. Although the patient's chemotherapy was not yet completed, the CHOP team pivoted quickly to adjust the plan so the patient could make the trip to HUP that day. Nurse Practitioner Jessica McWhorter, Fellow Rachel Hurley and Attending Jane Minturn adjusted the hydration plan, safely condensing several hours of hydration into just 30 minutes. Sarah Sexton accompanied the patient through each step and kept his care team informed and on track. Social Worker Sarah Brady stayed at the bedside to provide emotional support while Child Life Specialist Maddie Yeager calmly listened to the patient's fears and explained that the cancer affecting the grandfather was not the same as his own. Maddie also gave the patient a heart memento that was split in two – half for the patient to give to his grandfather and half for him to keep.
The patient was able to safely finish his treatment and travel to HUP with enough time to spend with his grandfather. He returned to CHOP with his half of the heart and his grandfather's hospital bracelet. The grandfather passed away later that day after having spent time with his favorite person in the world.
Days later, Ellen Tracy, VP & Associate Chief Nursing Officer, ran into the mother and son as they were being discharged. Even in her grief, the mother praised her son's care team, remembering many of them by name. "These people are amazing,” she said.
Rachel Most reflected, "In the hospital, it can be easy to get wrapped up in the way we always do things. That day, our oncology team was able to come together with a strong sense of shared purpose to do something extraordinary for this patient and family. I am so proud to be a part of this oncology team."
Heart to heart
A day in Oct. 2022 was much like any other day on the job for CHOP physician Stefanie Davidson, MD, associate professor of clinical ophthalmology and attending surgeon in the Division of Ophthalmology. Little did she know that her routine interaction with an 11-year-old patient had made a profound and lasting impact in the child's life. This particular patient, Alexa, had been seen by Dr. Davidson since she was an infant. Alexa had surgery with Dr. Davidson at the age of ten months to correct esotropia — or crossed eyes. She did well after surgery, and it wasn't until early 2022 that she came to see Dr. Davidson again because the esotropia had recurred, and she was experiencing double vision.
Dr. Davidson verified the amount of prism that would improve Alexa’s double vision, and she underwent her second surgery in Oct. 2022, almost ten years after her initial operation. At her postoperative appointment, the young patient earnestly shared with Dr. Davidson some concerns she had about comments that her classmates had been making about her red, recovering eyes, as well as comments that had been made about her misaligned eyes prior to the second surgery.
Dr. Davidson listened to Alexa’s concerns over the course of a long heart-to-heart conversation. She validated the patient's feelings and gave her examples of how to respond to negative comments from other people.
"I have a strong belief that since the child in front of me is the patient, I should be actively engaged with them during their visit," said Dr. Davidson. "I ask their opinions and try to hear a history from the child before I hear from their parents. Even though some patients are too young to articulate their feelings or convey their thoughts, I feel it's important that they understand I am here for them."
This respectful, compassionate approach to the pediatric patient was certainly not lost on Alexa or her mother.
"Dr. Davidson provided such attention and care to my daughter, and intently took the time to make her feel important and heard," said the patient's mom. "Most of all, she provided her with the most genuine feedback — my child walked out of that office with a smile and the confidence to conquer the world!"
She continued, "Dr. Davidson is not only an outstanding surgeon. She was also an amazing role model for my daughter that day. I truly believe that conversation will always remain in my daughter's heart, as well as mine."
Seeing ourselves in art
On October 27, 2022, CHOP social worker, Cherie Garrett-Debrest, MSW, attended the ribbon cutting ceremony for the new Center for Advanced Behavioral Healthcare at 4601 Market St. At this ceremony, Dr. Tami Benton, CHOP's Psychiatrist-in-Chief, gave a speech about the intentionality of placing this facility in the heart of West Philadelphia, with a promise to increase access to services for Black children, as well as to increase the ethnic diversity of the providers who serve them. In that moment, Cherie felt included and hopeful with the promise of greater diversity and inclusion.
Shortly after, Cherie took a tour of the building and visited the Department of Child and Adolescent Psychiatry and Behavioral Sciences (DCABPS) waiting room on the third floor, where a floor-to-ceiling mural of Philadelphia greets families, patients and staff. This mural is a map of iconic locations across the city and surrounding counties. "It is not only beautiful, but it invites you to explore the lives of the people who live, play and work here," Cherie said. "Then it hit me: something's missing. I was missing. The icons representing African Americans were missing."
Cherie saw the University of Pennsylvania, Drexel University and even Rutgers University in New Jersey. She didn't see institutions like Cheyney University, the first institution of higher learning for African Americans, or Lincoln University, the nation's first degree-granting historically black college. 4601 Market sits in zip code 19139 where the racial majority is 83% African American, and the lack of representation of this community in the artwork didn't sit right with Cherie.
She thought about the ICARE Value, Integrity, and decided she needed to speak up to be true to herself. “How can we claim to be intentional about diversity if the first thing that welcomes visitors does not include them?” Cherie reflected.
She brought this up to Kisha Hawthorne, SVP & Chief Operating Officer, CHOP Care Network, and Peter Grollman, SVP External Affairs, who listened and empathized. "I felt heard," Cherie remembered.
Before long, Cherie found herself on an email with leaders such as Gilbert Davis, Chief Diversity Officer; Lynne Tracy, Director of Facilities Project Management; and key project leadership members, including Jamie Huffcut, Director of Facilities Planning; and Jacqueline Simmers, Facilities Planner. Together, they made a list of the icons they'd like to see added to the mural to provide more cultural relevance and diversity. Once the list was final and approved by Dr. Benton, the artist went to work.
On July 7, 2023, the new mural was revealed, featuring 90 icons that represent the communities in CHOP's backyard. The mural is accompanied by a QR code that visitors can scan to learn about the importance of each icon. "You may ask, 'It's just art, what's the big deal?' Art inspires, it educates, it heals, it preserves history, and it acknowledges experiences. This is not only important to patients and families, but also to employees," Cherie said.
This was validated recently when Cherie again found herself in the third floor waiting room, chatting with Security Officer Robert Haynes, who did not know Cherie or her connection to the refreshed artwork. He called her over and proceeded to tell Cherie the story of why the mural was changed and how he saw himself represented in the new version.
"This just goes to prove that when employees are engaged, even if it's just sharing an observation, it makes CHOP a better place for all," Cherie concluded.
CHOP’s global impact on pediatrics
In 2008, CHOP's Department of Radiology established a partnership with Tikur Anbessa/Black Lion Specialized Hospital (TASH)/Addis Ababa University (AAU) in Addis Ababa, Ethiopia to support pediatric radiology education for its residents. This partnership led to the establishment of the CHOP-AAU Pediatric Radiology Fellowship Program at TASH, which is a two-year fellowship – the first of its kind worldwide.
Dr. Hansel Otero, Director of Global Radiology Outreach and Education, is one of many CHOP staff members working on growing this partnership and enabling its success. The outreach program works with AAU, TASH and the Radiological Society of Ethiopia (RSE) and has received more than 50 CHOP staff.
Until 2017, there were no pediatric radiologists in the country, but thanks to this fellowship program, there are now five pediatric radiologists, out of the 350 practicing radiologists in a country with 120 million people, 40% of whom are children.
This outreach focuses on day-to-day teaching for radiology residents, the two-year fellowship program, and hosting CME events for practicing radiologists, where radiologists from all over the country come together for refresher courses and updates on the practice of pediatric radiology.
Dr. Otero highlights two important changes because of this fellowship program. First, in 2014, the CHOP team introduced non-surgical intussusception reduction, which is a technique to avoid surgery in patients, usually toddlers, with small bowel obstruction due to the bowel "telescoping" into itself. Not only is this technique safer, but it yields better outcomes and a faster discharge time. Two other provincial Ethiopian hospitals began using this technique after residents from the CHOP-AAU program taught it at those locations.
The second highlight is the recruitment of CHOP-trained faculty as supporting faculty for a new radiology residency program in Malawi, the first in the country. The program in Malawi recruited CHOP-AAU faculty with teaching and curriculum design experience to assist and help organize the newfound program. This is a huge accomplishment for the partnership.
Accelerating breakthroughs
CHOP researchers are dedicating the resources necessary to develop, test and bring to the bedside a single gene therapy for an ultra-rare condition that affects only 30 to 40 patients around the world as part of the Accelerating Medicines Partnership Bespoke Gene Therapy Consortium (AMP BGTC).
Rebecca Ahrens-Nicklas, MD, PhD, physician scientist in the Division of Genetics, and Laura Adang, MD, PhD, MSTR, attending physician in the Division of Neurology, will lead the AMP BGTC study site for multiple sulfatase deficiency (MSD), an ultra-rare and devastating condition that robs children of their neurologic function. Their study team is among a select group who received grant support from the Foundation for the National Institutes of Health (FNIH) to develop first-in-human gene therapy trials and build a knowledge base about how to move gene therapies forward for eight rare conditions. The unique public-private partnership includes academic and industry leaders, the National Institutes of Health and the U.S. Food and Drug Administration.
"What we learn from our roadblocks and successes in this model can be applied to the thousands of other ultra-rare conditions for which people are trying to develop gene therapy," Dr. Ahrens-Nicklas said. "It is an unprecedented opportunity to dismantle barriers and optimize care not only for MSD, but all rare diseases."
The BGTC will develop a rare disease clinical trial playbook that includes ideas for preclinical testing models, best practices for manufacturing a vector, and tips on how to interact with the FDA. This learning will occur in the public domain to increase the level of transparency about how to successfully take a gene therapy program through Investigational drug application and approval.
Drs. Ahrens-Nicklas and Adang's work with the AMP BGTC is grounded in years of learning, relationship-building with patients and families and collaboration with like-minded investigators. The colleagues-turned-friends first met each other at a pediatric residency welcome event, and they developed a shared interest in MSD, a genetic disorder that affects the SUMF1 gene.
MSD reduces the function of the formylglycine-generating enzyme which, in turn, affects the function of all cellular sulfatases. The resulting accumulation of molecular byproducts causes an ultimately fatal breakdown of the body, and there is currently no treatment available. Based on genotype and residual enzyme activity, there is a spectrum of clinical severity affecting children with MSD, ranging from attenuated to severe disease.
Drs. Ahrens-Nicklas and Adang launched a formal natural history study with the Leukodystrophy Center of Excellence at CHOP which serves as the study's clinical home. The researchers gather information about MSD disease progression through medical records with urine and blood samples. Participants who receive clinical care at CHOP are invited to receive optional physical and occupational therapy assessments.
The symptoms of MSD, including neurologic deterioration, heart disease, hearing loss and airway compromise, are progressive. A child may be developing along a typical trajectory, then quickly lose neurologic function over one to two years.
The natural history study has helped researchers to develop ways to predict and identify patients who are more likely to be in a severe group versus a less severe group, which Dr. Ahrens-Nicklas described as a game-changer. The researchers now have biomarkers that correlate to their findings about each patient's genetic change and the basic milestones children with MSD do or do not meet early on.
"We have learned so much about the genetics, biochemistry, and clinical progression of this disease," Dr. Ahrens-Nicklas said. "We are now able to evaluate a child early on and have a better understanding of how that child will be presenting in three to five years. Without that knowledge, we would not have been ready for a clinical trial. The effort over the past six years to compile that data in parallel with lab work to develop the gene therapy approaches came together at the right time for us to be able to successfully compete for the Bespoke grant."
Currently available clinical data support an in vivo gene therapy approach. Once underway, the clinical trial will use an adeno-associated viral vector to deliver gene replacement therapy into the cerebrospinal fluid to target the neurologic manifestations of MSD.
"We will first try this in vivo approach and hope that it is successful," Dr. Adang said. "But if it is not, we will be able to use that same comparator arm, which we have rigorously designed and curated, as a control for future clinical trials."
Prior knowledge about lysosomal storage diseases and leukodystrophies underscores the importance of early intervention to prevent disease progression in the brain. As they design a gene therapy trial and work toward definitive therapy, the researchers also aim to find ways of diagnosing children early and even pre-symptomatically.
MSD has the potential to be found through newborn screening, which often includes measurement of enzyme activity. It is the multiplicity of enzyme deficiencies that raises a red flag for MSD, since the condition affects enzyme function across all sulfatases.
"Families point to the journey to diagnosis as being the most stressful time," Dr. Adang said. "Irrespective of the development of transformative therapies, it's important to be able to guide families and triage care for them. More definitive newborn screening can give us an answer and guidance. Since we're also working on therapy at the same time, we can also give hope."
Dr. Ahrens-Nicklas and Dr. Adang credit the collaborative infrastructure at CHOP for support throughout the BGTC process. Chief Scientific Strategy Officer Beverly Davidson, PhD, first introduced the researchers to a parent of a child with MSD who was in search of scientific partnership and became a close friend. The Clinical In Vivo Gene Therapy team was instrumental to completing their grant application, and the Cell and Gene Therapy Collaborative provided support that moved their work forward.
In addition to their CHOP colleagues, the researchers are grateful to Lars Schlotawa, MD, international medical director of the United MSD Foundation, their partner for "all things natural history and for MSD trial design," and applaud Stephen Gray, PhD, director of the Translational Gene Therapy Core at UT Southwestern, and Rachel Bailey, PhD, for their development of the AAV9 MSD vector and critical pre-clinical animal model work to the benefit of the MSD community.
Most of all, Dr. Ahrens-Nicklas and Dr. Adang are thankful for the families who donate their time and effort so researchers can learn about each child and their disease progression.
"The families we have met find great meaning in being able to share their child's story and clinical features, because they know how important it is for the next generation of patients who are diagnosed with MSD," Dr. Adang said. "The opportunity to participate in the natural history study provides purpose to the families' journey with this disease and gives their child a legacy — they will not be forgotten."
Exam room education empowers safety
The Gun Safety Program started with curiosity. Two pediatric trainees noticed during their rotations in the Emergency Department (ED) that staff were counseling people on safe firearm storage and handing out gun lock devices at the point of care. These trainees approached Dorothy Novick, Attending Physician at South Philadelphia Primary Care and a Practice-based Scholar for the Center for Violence Prevention (CVP), and asked about starting a similar program in South Philadelphia. It was a great idea: delivering information in the exam room that's proven to reduce suicides and unintentional shootings.
Dorothy partnered with Joel Fein, MD, MPH, Attending and Director, Advocacy and Health Policy, who was leading this work in the ED and is co-director of CVP, and the Epic team to build in a prompt in Epic to remind providers to ask about firearms during the pediatric well visit. The team also contacted the Philadelphia Sheriff's Department, which gave CHOP 500 free gun locks. The locks were distributed along with education materials to the Philadelphia Primary Care teaching practices: Karabots, South Philadelphia and Cobbs Creek. Dorothy and her team created and provided a provider training session so that everyone felt prepared to have what we know can be a very sensitive, though life-saving, conversation with patient families.
In Jan. 2021, when providers had been trained, the Epic prompt was turned on and this pilot took off. By March 2021, all 500 gun locks had been handed out. From there, the Office of Government Affairs helped with funding to acquire additional gun locks, and the Gun Safety team turned the Epic prompt on for all annual well visits. Then, Dorothy, Joel and program manager Kimberly Sterner-Stein and their team were awarded a Chair's Initiative grant, allowing the program to expand, test and refine the intervention across a variety of ambulatory and inpatient care settings. The goal is to create an evidence-based, standardized and fully adaptable program that can be used across the range of healthcare settings at CHOP.
The Gun Safety Program has now expanded and established partnerships with The Possibilities Project, Adolescent Initiative, Pediatric ICU, the Injury Prevention Program, the Office of Community Impact and CHOP's Security team.