Abstract

X-linked agammaglobulinemia (XLA), or Brutons disease, is the most common human primary humoral immunodeficiency. XLA is caused by mutations of the Brutons tyrosine kinase (BTK), a key regulator of B-cell physiology. Since the mid 80s, substitutive therapy by intravenous gammaglobulin infusions has significantly improved XLA patient survival and quality of life. Nevertheless, some frequent affections persist despite treatment, and lead to handicapping and further to morbid clinical complications for XLA individuals. Development of gene therapy by transfer of the BTK gene into hematopoietic progenitors could represent an alternative strategy for the treatment of Brutons disease, with the advantage of a definitive cure for XLA patients. Gene therapy of XLA could be considered as a paradigm for future expansion of gene therapy approaches for many other diseases, since future utilization may be strictly dependent on a marked improvement of risk-benefit ratio compared to pre-existing treatments.

Keywords: Bruton's disease, BTK, Immunodeficiency, B-cell, Retroviral vector, Hematopoietic stem cell