DFT383

DFT383 involves extracting a patient’s hematopoietic stem cells, genetically modifying them ex vivo with a lentiviral vector to insert a functional CTNS gene, and reinfusing them after myeloablation. The modified cells are intended to produce functional cystinosin, a lysosomal cystine-proton symporter, reducing cystine accumulation throughout the body, including in the kidneys, eyes, and other organs. In preclinical studies using Ctns−/− mice, treatment with lentiviral-based CTNS gene therapy resulted in significant reductions in tissue cystine levels and preservation of kidney, eye, and thyroid function. == Development history ==

DFT383 was initially developed by AVROBIO as AVR-RD-04, with early clinical trials sponsored by the University of California, San Diego. A Phase I/II trial, approved by the FDA in November 2018, enrolled six adult patients and showed sustained engraftment, reduced leukocyte cystine levels, and improvements in visual and motor functions up to 36 months post-treatment, with patients discontinuing oral cysteamine. No serious adverse events related to the therapy were reported. ==References==