New treatment for leukocyte adhesion deficiency type 1 (LAD1)

2017

Challenge

Leukocyte adhesion deficiency type 1 (LAD1) is a genetic disorder that weakens the immune system, leading to frequent infections and loss of teeth before adulthood. LAD1 patients have mutations in the gene ITGB2, which encodes an important building block of a family of proteins called β2 integrins that are required for the proper function of immune cells called neutrophils. Currently, the only cure for LAD1 is hematopoietic stem cell transplantation, which remains a risky procedure with serious health complications of its own.

Advance

IRP researchers led by Niki M. Moutsopoulos, D.D.S., and Steven M. Holland, M.D., treated an LAD1 patient with ustekinumab, an antibody used in the treatment of psoriasis, which blocks signaling by the immune system molecules interleukin-23 and interleukin-12. After treatment, the patient’s infections resolved and their levels of inflammation and infection-induced tissue damage reduced without serious infections or adverse reactions.

Impact

A clinical trial of ustekinumab for the treatment of LAD1 patients has been initiated at the NIH Clinical Center (NCT023366142) to test the safety and tolerability of the therapy in additional patients. If successful, the team’s research may lead to a safer, effective treatment for people living with LAD1.

Publications

Moutsopoulos NM, Zerbe CS, Wild T, Dutzan N, Brenchley L, DiPasquale G, Uzel G, Axelrod KC, Lisco A, Notarangelo LD, Hajishengallis G, Notarangelo LD, Holland SM. (2017). Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1. N Engl J Med. Mar 23;376(12):1141-1146.