Adenosine deaminase deficiency: current treatments and emerging therapeutics

作者：Kim Vy Hong-Diep; Murguia-Favela Luis; Grunebaum Eyal^*

来源：Expert Opinion on Orphan Drugs, 2018, 6(2): 117-125.

DOI：10.1080/21678707.2018.1418660

• Adenosine deaminase deficiency
• enzyme replacement therapy
• gene therapy
• hematopoietic stem cell transplantation
• polyethylene glycol
• severe combined immune deficiency

Introduction: Adenosine deaminase (ADA) deficiency is a systemic metabolic disorder characterized by severe immune and non-immune abnormalities and is often fatal in infancy. ADA deficiency can be treated by allogeneic hematopoietic stem cell transplantation (HSCT), ADA enzyme replacement therapy (ERT) or ex vivo gene therapy (GT).
Areas covered: This article discusses the different treatment options currently available for ADA deficiency, remaining challenges and expected developments.
Expert opinion: Experts in ADA deficiency should manage this complex disease, as a patient's individual factors often determine treatment course. Unconditioned HSCT from an HLA identical sibling is the preferred option. ERT can provide short-term benefits for patients without such donors, or until other definitive treatments are established. Commercial gamma-retrovirus GT, currently available only in Italy, or investigational lentivirus GT have, to date, been shown to be safe, although long-term follow up is needed to determine their continued effectiveness. Therefore, GT should be considered for patients without an appropriate HSCT donor and when families are able to travel to Italy or participate in research protocols. Additional studies into the pathogenesis of ADA deficiency and the effects of the different treatment modalities will assist in determining the ideal management for individual patients.

• 出版日期2018