Gene Therapy for Nephropathic Cystinosis

Cystinosis is a prototypical lysosomal storage disease caused by recessive pathogenic variants in CTNS , which encodes cystinosin, a ubiquitous proton-driven lysosomal cystine transporter. 1 Loss of cystinosin leads to intralysosomal cystine accumulation, impaired lysosomal signaling, defective autophagy, and widespread cellular dysfunction. 2-4 The most severe and common form, nephropathic cystinosis, manifests in infancy with proximal tubular dysfunction (renal Fanconi’s syndrome) and progresses to chronic kidney disease. Cystine crystal deposition in the cornea causes photophobia and painful erosions. Systemic complications from cystine accumulation include hypothyroidism, hypogonadism, diabetes, myopathy, and progressive neurologic involvement. 5 Beyond supportive measures, cysteamine remains the only disease-specific therapy. By depleting . . .