Therapeutic strategies in cystinosis: A focus on cysteamine and beyond

Cystinosis is a autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene, which encodes cystinosin, a cystine transporter. The defective function of cystinosin leads to cystine accumulation in the lysosome, resulting in progressive multi-organ damage. Cystinosis manifests early in life, with nephropathic cystinosis typically presenting in infancy with renal Fanconi syndrome, leading to chronic kidney disease and end-stage renal disease if untreated. Diagnosis relies on clinical evaluation, corneal examination, leukocyte cystine quantification, and CTNS genetic testing. In the present review, both cysteamine-based and non-cysteamine therapeutic approaches for the treatment of cystinosis are discussed. Cysteamine therapy, reduces intracellular cystine levels and delays disease progression, significantly improving patient outcomes. However, cysteamine requires lifelong adherence and has limitations, including gastrointestinal side effects and frequent dosing. Kidney transplantation remains a therapeutic option for end-stage renal disease, although extra-renal complications persist. Novel therapeutic strategies are under investigation to address these limitations, including improved cysteamine formulations, prodrugs, and small molecules. Additional approaches include gene therapy, stem cell-based interventions, mRNA-based treatments, and the targeted degradation of cystine crystals. Continued research and multidisciplinary management are essential to enhancing the prognosis and quality of life for individuals affected by cystinosis.