Boztug Kaan, Dewey Ricardo A, Klein Christoph
Department of Pediatric Hematology/Oncology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
Curr Opin Mol Ther. 2006 Oct;8(5):390-5.
Wiskott-Aldrich syndrome (WAS) is a complex primary immunodeficiency disorder associated with microthrombocytopenia, autoinnmunity and susceptibility to malignant lymphoma. At the molecular level, this rare disorder is caused by mutations in the gene encoding the Wiskott-Aldrich syndrome protein (WASP). WASP is a cytosolic adaptor protein mediating the rearrangement of the actin cytoskeleton upon surface receptor signaling. Allogenic hematopoietic stem cell (HSC) transplantation represents a curative approach but remains problematic in light of severe risks and side effects. Recently, HSC gene therapy has emerged as an alternative treatment option. Cumulative preclinical data obtained from WASP-deficient murine models and human cells indicate a marked improvement of the impaired cellular and immunological phenotypes associated with WASP deficiency. The first clinical trial is currently being conducted to assess the feasibility, toxicity, and potential therapeutic benefit of transplanting autologous WASP-reconstituted hematopoietic stem cells.
威斯科特-奥尔德里奇综合征（WAS）是一种复杂的原发性免疫缺陷疾病，与微血小板减少症、自身免疫和恶性淋巴瘤易感性相关。在分子水平上，这种罕见疾病是由编码威斯科特-奥尔德里奇综合征蛋白（WASP）的基因突变引起的。WASP是一种胞质衔接蛋白，在表面受体信号传导时介导肌动蛋白细胞骨架的重排。同种异体造血干细胞（HSC）移植是一种治愈方法，但鉴于严重风险和副作用，仍然存在问题。最近，HSC基因治疗已成为一种替代治疗选择。从WASP缺陷小鼠模型和人类细胞获得的累积临床前数据表明，与WASP缺陷相关的受损细胞和免疫表型有显著改善。目前正在进行第一项临床试验，以评估移植自体WASP重组造血干细胞的可行性、毒性和潜在治疗益处。
