Gene Therapy for Wiskott-Aldrich Syndrome

A Phase I/II Clinical Trial of Hematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome

This is phase I/II protocol to evaluate the safety and efficacy of WAS gene transfer into hematopoietic stem/progenitor cells for the treatment of Wiskott Aldrich Syndrome.

Wiskott-Aldrich Syndrome (WAS) is an X-linked primary immunodeficiency caused by mutations in the WAS gene which encodes the WAS protein (WASP), a cytoskeletal regulator which is expressed exclusively in hematopoietic cells.

Inclusion Criteria:

1. Diagnosis of WAS defined by genetic mutation and at least one of the following criteria:

   • Severe WAS mutation
   • Absence of WASP expression
   • Severe clinical score (Zhu clinical score ≥ 3

2. No HLA-identical sibling donor

3. Negative search for a matched unrelated donor (10/10) or an adequate unrelated cord blood donor (5-6/6) within 4-6 months

   • Patients of > 5 years of age who are not candidate to unrelated allogeneic transplant based on clinical conditions.

4. Parental/guardian/patient signed informed consent.

Exclusion Criteria:

1. Patients positive for HIV-infection.
2. Patients affected by neoplasia.
3. Patients with cytogenetic alterations typical of MDS/AML.
4. Patients with end-organ functions or any other severe disease which, in the judgement of the investigator, would make the patient inappropriate for entry into this study.
5. Patients who underwent an allogeneic haematopoietic stem cell transplantation in the previous 6 months.
6. Patients who underwent an allogeneic haematopoietic stem cell transplantation with evidence of residual cells of donor origin.