Calls Now Open
2027 Scholar-Innovator and ADDF-Harrington
Rare/Orphan, Metabolic, Nephrology
A Life-Saving Treatment for Sphingosine-1-Phosphate Lyase Insufficiency Syndrome (SPLIS)
2024 Harrington Scholar-Innovator
Dr. Saba trained as a cancer doctor and researcher, but when she first encountered sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS), she knew it was the disease she was meant to face.
“The need seemed so obvious. I immediately incorporated it into my research goals,” she says. “I realized there could be no better purpose for me.”
Dr. Saba picked a tough foe. SPLIS is a rare and deadly kidney disorder. The disease mostly affects children, and infantile SPLIS carries a 70% mortality rate by age five. There is no cure; kidney transplantation represents the only lifesaving intervention.
SPLIS is caused by a mutation in a single gene. Dr. Saba explains that once the gene has mutated, it becomes inactive and no longer can encode sphingosine-1-phosphate lyase (SGPL1), an enzyme that is essential to sphingolipid metabolism. Sphingolipids are a class of lipids that perform crucial roles in cells, including regulating processes such as cell growth and death.
Dr. Saba discovered the first SPLIS gene and has been studying its function in various model organisms. Now, she and her team have developed a potentially curative intervention: adeno-associated virus-mediated SGPL1 gene therapy (AAV-SPL).
“AAV-SPL addresses the root cause of SPLIS,” she says. “We have established proof-of-concept in a mouse model and are now exploring ways to optimize the efficacy and potency of AAV-SPL.”
With the support of Harrington Discovery Institute, Dr. Saba hopes to create an armamentarium of treatments that can be personalized for each patient.
“All of our efforts are worthwhile simply because every child is unique and beautiful,” she says.
"Rare diseases often unlock the puzzles to much more common diseases by teaching us the genes and the pathways that are involved in their physiology."