ABOUT THE GRANT

Krabbe disease is a rare and devastating genetic condition with limited treatment options. This project aims to develop a safer and more
effective therapy using the patient’s own stem cells. The therapy, called human GALC-HSPCs, involves taking blood-forming stem cells from
a patient and modifying them in the lab using advanced gene-editing techniques. A healthy version of the defective Krabbe disease (GALC)
gene is added to the cells. These modified cells can then be returned to the patient to deliver GALC to the brain and nervous system, where
it is needed to slow or stop the disease.

This approach improves the current treatment, which involves using stem cells from donors (called allogeneic stem cell transplants).
Donor stem cell treatments carry significant risks, such as rejection, and only provide limited benefits. By using the patient’s cells, this new
therapy avoids those risks and is designed to deliver the enzyme to affected tissues much more effectively.

The project will follow a three-year plan to develop and test this therapy. In the first year, we will refine the process for editing the patient’s
cells to ensure it is safe and efficient. In the second year, we will test how well the modified cells grow and work in mice, ensuring they can
survive, multiply, and deliver the enzyme to the right places. In the third year, we will test the therapy in mouse models of Krabbe disease to
see how well it reduces symptoms and improves outcomes.

This research will address the significant challenges in treating Krabbe disease by creating a safer and more effective therapy
than current options. It will also pave the way for similar treatments for other diseases and move us closer to personalized therapies
for genetic conditions.

Dr. Natalia Gomez-Ospina is an Assistant Professor of Pediatrics (Medical Genetics) atStanford University and a board-certified medical geneticist. As a physician-scientist, she bridges clinical care and laboratory research to improve the diagnosis and treatment of lysosomal storage disorders, including Krabbe disease. At Lucile Packard Children’s Hospital, she leads the enzyme replacement therapy service and directs the Stanford Medicine Children’s Health – NORD Center of Excellence for Rare Disorders, advancing gene- and cell-based therapies for children with rare genetic conditions.

Dr. Gomez-Ospina’s research focuses on harnessing the hematopoietic system to deliver lysosomal enzymes to the brain, addressing one of the most critical challenges in treating neurodegenerative lysosomal diseases like Krabbe. Her laboratory has developed an adaptable genome-editing platform for autologous transplantation of corrected hematopoietic stem cells, enabling systemic and central nervous system enzyme delivery. This approach is being applied to Mucopolysaccharidosis type I (Hurler syndrome), Gaucher disease, and now Krabbe disease.

Although early in her career, Dr. Gomez-Ospina has made significant scientific contributions, with publications in The New England Journal of Medicine, Cell , Nature Communications , and the American Journal of Medical Genetics . Her work has been recognized through numerous awards, including the Genetics and Genomic Medicine Innovation Award from the ACMG, the Outstanding Young Investigator Award from ASGCT, the Young Scientist Award from ASCI, the Young Investigator Award from WSPR, and the William K. Bowes Jr. Award in Medical Genetics from Partners HealthCare Personalized Medicine.