For children born with a rare and often lethal immune disorder, a viable treatment has historically depended on finding a perfectly matched sibling donor — an option unavailable to most families. The first FDA approval of a gene therapy that bypasses this requirement represents a meaningful advance for a condition where the mortality rate in severe cases can reach 60–75% within the first two years of life without definitive intervention.
Marnetegragene autotemcel, now approved under the brand name KRESLADI, targets leukocyte adhesion deficiency type I (LAD-I), a monogenic disorder caused by biallelic loss-of-function variants in the ITGB2 gene. ITGB2 encodes the beta-2 integrin subunit (CD18), a protein essential for white blood cells to exit the bloodstream and reach sites of infection. Without functional CD18, neutrophils cannot adhere to vascular endothelium, rendering patients profoundly susceptible to life-threatening bacterial and fungal infections. The therapy works by harvesting the patient's own hematopoietic stem cells, inserting functional ITGB2 copies via a lentiviral vector, and reinfusing the corrected cells — avoiding the graft-versus-host disease risk inherent in allogeneic transplantation.
This approval sits within a rapidly maturing era of ex vivo stem cell gene therapies, following earlier successes in ADA-SCID and sickle cell disease. The autologous approach is particularly compelling for LAD-I because allogeneic transplant outcomes are highly dependent on donor match quality and timing. Key limitations remain: LAD-I affects an extremely small patient population, meaning clinical trial cohorts are necessarily limited, and long-term durability of engraftment and gene expression beyond a few years is still being characterized. Manufacturing complexity and cost will also constrain access. Nevertheless, as a curative-intent therapy for a monogenic disease with no adequate pharmacological alternatives, this approval is clinically significant rather than merely incremental.