Leukocyte adhesion deficiency (LAD)

Treatment

The mainstay treatment is the aggressive use of antibiotics to treat the repeated infections associated with LAD. Individuals with moderate or mild forms of LAD1 or LAD2 usually respond to prompt antibiotic treatment for episodes of acute infection. Preventive or prophylactic antibiotic therapy may be advisable for individuals with LAD1.

In rare cases, transfusions of neutrophils (the white blood cells most affected in LAD) may help treat life-threatening infections. However, these are not widely available and should be used only in severe cases when all other therapeutic options have failed. Blood transfusions are required for individuals with LAD3 who experience severe bleeding episodes.

The only corrective therapy for individuals with LAD1 and LAD3 is hematopoietic stem cell transplantation. Stem cell transplants can correct the genetic variants of the white blood cells and are recommended early in life if possible. The initial results of stem cell transplants for individuals with severe LAD1 have been very encouraging. Overall survival of individuals with LAD1 who have had a stem cell transplant is almost 75%.

Supplementation with fucose, a form of sugar, is being investigated as a way to treat individuals with LAD2. A few patients have had significant improvement in symptoms, including the prevention of recurrent infections. However, not all patients respond to fucose supplementation. Further research is necessary to determine the long-term safety and effectiveness of this treatment strategy.

In 2026, the U.S. Food and Drug Administration (FDA) approved marnetegragene autotemcel (trade name Kresladi). Kresladi is a gene therapy for children with LAD1 who do not have a matched sibling donor for HSCT.

Whereas HSCT replaces a person’s hematopoietic stem cells, the goal of gene therapy is to modify the DNA within stem cells. Correcting stem cells through gene therapy allows the person to make healthy immune system cells, as well as red blood cells and platelets, providing people with LAD1 with working immune systems.

Kresladi uses a hollowed out virus, called a lentiviral vector, to add a working copy of the ITGB2 gene to stem cells that have been removed from the affected person’s body. The modified cells are then returned to the person through an IV infusion.

There are several advantages to gene therapy versus HSCT. First, there is no need to find a donor, so even people who do not have a good donor available can be treated. Second, since the person’s own cells are modified, there is no risk for graft-versus-host disease. Finally, in general, gene therapy requires less conditioning than HSCT.

It is important to remember that gene therapy, like HSCT, cannot reverse existing organ damage. In addition, people who have been treated successfully with gene therapy can still pass on their ITGB2 gene variant to their biological children.