Breakthrough in Understanding Rare Multi-Organ Disease Unveils New Pathways for Treatment

A team of researchers from Duke-NUS Medical School has unraveled the mystery behind a rare and previously undiagnosed multi-organ disease. This discovery provides crucial insights into the disease's root cause and opens new avenues for targeted therapies.

Published in the Journal of Clinical Investigation, the study identified mutations in the gene SPNS1 as the cause of the disorder. This gene plays a vital role in cellular recycling processes, specifically in how cells manage fat molecules. Faulty versions of SPNS1 hinder the function of lysosomes—the cellular waste disposal system—leading to an abnormal accumulation of fats and cholesterol. This buildup results in progressive damages to the liver and muscles, characteristic of the disease.

The condition belongs to the lysosomal storage diseases, a collection of over 70 rare disorders caused by defective cellular recycling. The research was prompted by analyzing two unrelated families where children exhibited unexplained liver and muscle issues. Genetic analyses revealed both children carried mutations in both copies of the SPNS1 gene.

Building on previous studies, the researchers demonstrated that SPNS1 is essential for transporting broken-down phospholipids out of lysosomes. These lipids are important for cell membrane repair and energy storage. When this transport is disrupted, tissue damage worsens, especially under conditions where cells are responding to nutrient stress.

Professor David Silver emphasized that SPNS1 is universally present in human cells and is central to maintaining lipid balance. The findings suggest that this gene’s role in lipid homeostasis could be relevant in other diseases such as cancer.

The research team is collaborating with the N = 1 Collaborative to translate these insights into personalized treatments. One promising approach involves genetic therapies aimed at correcting fat transport defects. The hope is that these advances will lead to better management options and improved quality of life for affected families.

Family members, including mother Dalila Sabaredzovic, expressed optimism that these scientific breakthroughs are paving the way toward potential cures and enhanced care options. Medical experts at Duke-NUS underscore that understanding genetic causes enables precision medicine, offering hope to patients with rare and complex diseases.

This discovery exemplifies how integrating genetic research and clinical application can unlock new possibilities for treating even the most elusive conditions.