Cord Blood Transplantation is a Critical Treatment for Babies and Children with Inherited Metabolic Disease

When ZA was born in late March 2024 in Minnesota, his arrival coincided with the recent addition of Infantile Krabbe Disease (IKD) to the Recommended Uniform Newborn Screening Panel, which was passed by the Advisory Council on Heritable Diseases in Children in February 2024 and signed by the Secretary of Health and Human Services in July of 2024. Just weeks before Zion’s birth, the state of Minnesota had implemented universal screening for IKD. Krabbe Disease is a rare and devastating inherited leukodystrophy. Leukodystrophies are a rare group of disorders that damage the protective covering, called myelin, around the nerves in the brain and spinal cord. When myelin is damaged or doesn’t develop properly, it causes serious problems with movement, thinking, and other body functions. Leukodystrophies are often fatal in infancy or childhood. 

When he was 6 days old, Zion’s mother, Kristina, received the life-altering news that her newborn son had tested positive for IKD through Minnesota’s newborn screening program. IKD, caused by mutations in the gene encoding the enzyme galactocerebrosidase (GALC) results in a deficiency of the enzyme leading to accumulation of a toxic metabolite called psychosine in the central nervous system, leading to severe demyelination, neurodegeneration, and death in the first 2 years of life. Babies with untreated IKD develop feeding problems, failure to thrive, developmental delay, extreme irritability, spasticity, seizures, and blindness in the first 6-12 months of life. The only treatment for babies with IKD is an unrelated donor umbilical cord blood transplant. Results are best if the transplant is performed before 30 days of age.  The addition of IKD to newborn screening panels gives these babies a chance at life. 

Kristina was informed that Zion’s best—and only—chance for survival was a hematopoietic stem cell transplant (HSCT) with an unrelated umbilical cord blood donor before the onset of symptoms, ideally within the first 30 days of life. Kristina was instructed to immediately bring Zion to the University of Minnesota Masonic Children’s Hospital, where their dedicated pediatric blood and marrow transplantation team took charge of his care. On April 19, 2024, at just 25 days of age, Zion underwent a 7/8 match unrelate donor umbilical cord blood transplant. His cord blood donor unit was sourced from the US FDA licensed public cord blood bank.  Zion engrafted with donor cells 19 days after his transplant signifying that the transplant was a success. After weeks of specialized care, Zion was initially discharged from the hospital on May 24, 2024, marking a significant milestone in his journey.  He did have to be readmitted for treatment of bacterial sepsis, CMV, and a pericardial effusion but he ultimately stabilized over the next couple of months. 

After recovering from his transplant, Zion was referred to Duke to participate in a novel gene therapy trial for babies with Krabbe Disease post transplantation. The gene therapy, FBX-101, an AAV-10 gene therapy developed by Forge Biologics. Preclinical studies have demonstrated that FBX-101 improves myelination, restores gross motor function, and significantly prolongs lifespan in animal models.  Most importantly, it helps prevent peripheral nervous system disease which is not corrected by transplant alone. 

In the fall of 2024, Zion and Kristina traveled to Duke University where he underwent extensive evaluation to determine his eligibility for FBX-101. On October 23, 2024, he received the groundbreaking gene therapy, marking a new chapter in his journey. He was the first baby to receive the higher dose per the phase 1 protocol he was enrolled on. He has done very well and will be followed on the Forge study for the next 2 years. 

Zion quickly captured the hearts of the staff at Duke. During his frequent port accesses—a procedure typically unenjoyable for most—Zion smiles and coos at the nurses as long as he is served TootSweet, a sugar water treat that never fails to brighten his mood. Whether wearing his tiny eye mask to block the fluorescent hospital lights during naptime or flashing his infectious grin, Zion’s personality continues to shine through, bringing joy to everyone he meets. Zion’s journey is a testament to the power of early diagnosis and medical innovation. From the swift action prompted by newborn screening to the challenges of an unrelated cord blood transplant in a newborn, and the hope offered by gene therapy, Zion’s story reflects the resilience of one little boy and the remarkable strides being made in the fight against rare diseases like Krabbe. 

Krabbe disease is an example of a class of genetic diseases that can benefit from hematopoietic stem cell transplantation using unrelated umbilical cord blood donors.  Transplant is most successful if performed early in the course of disease, even before clinical symptoms develop.  For this reason, testing for these diseases is being added to newborn screening panels in states in the USA.  The standard of care for babies identified through newborn screening is an unrelated donor umbilical cord blood transplant early in life. Cord blood is an ideal donor source for these patients because it is (“off-the-shelf”, available within 5 days), can be tested for carrier status for the disease the patient is being transplanted for (if indicated), contains more cells than adult donor sources that migrate to brain. While rare diseases are a small market overall, when combined, this has the potential to increase cord blood transplantation by dozens of transplants per year in the USA.