Seoul St. Mary's Hospital researchers demonstrate gene editing for rare kidney disease

A research team led by Professor Jeong Byeong-ha of the Department of Nephrology at Seoul St. Mary's Hospital has demonstrated the potential to treat Gitelman syndrome, a rare genetic kidney disorder, using CRISPR/Cas9 gene-editing technology.

Gitelman syndrome occurs in approximately 1 in 40,000 people and is caused by mutations in the SLC12A3 gene, which prevents the kidneys from properly reabsorbing sodium and chloride. This leads to electrolyte imbalances that can cause fatigue, arrhythmia, cardiac arrest, and muscle paralysis. Currently, treatment is limited to symptomatic electrolyte replacement.

The researchers created induced pluripotent stem cells from two patients with different mutations and inserted a complete, functional SLC12A3 gene into a 'safe harbor' site on the chromosome. When these corrected cells were grown into kidney organoids, the protein levels for sodium and chloride transport rose to approximately 90% of normal levels. The organoids also regained physiological responsiveness to angiotensin II and thiazide diuretics.

While the study provides a proof-of-concept for a universal treatment that could work regardless of specific patient mutations, the team noted that further research is required to verify long-term safety and efficacy in animal models before clinical application.