The Wiskott-Aldrich syndrome (WAS) is a disease of profound thrombocytopenia and severe immune defects caused a defective X chromosome gene. Signs and symptoms include easy bruising or bleeding due to a decrease in the number and size of platelets; susceptibility to infections and to immune and inflammatory disorders; an increased risk for lymphoma; and eczema. WAS is caused by genetic changes in the WAS gene and is inherited in an X-linked manner. WASp (protein encoded by the WAS gene) regulates the cytoskeleton in hematopoietic cells, which is required for many functions of T cells and B cells. Mutations in the WAS gene lead to B cell dysfunction, small platelet size with abnormal morphology, and further decrease of the platelet count caused by the trapping and destruction of platelets in the spleen.
There is no effective treatment for WAS, and current therapies only aim to relieve the symptoms. Most children with severe Wiskott-Aldrich syndrome die before the age of 15. Allogeneic hematopoietic stem cell transplantation offers the opportunity of cure for all these complications. However, the difficulty of finding donors and the risks of graft versus host disease greatly limit the implementation of allogeneic hematopoietic stem cell transplantation.
Gene therapy based on gene edited autologous hematopoietic stem cells can effectively avoid the aforementioned problems. Gene therapy can also achieve a more effective expression of the target gene. Clinical trials carried out in EU and US have verified the feasibility of this therapy and has made gratifying progress.
