Gene therapy for adenosine deaminase deficiency

Area of Science:

• Hematology
• Immunology
• Gene Therapy

Background:

• Gene transfer into hematopoietic cells has advanced from experimental procedures to clinical applications.
• Severe combined immunodeficiency disease (SCID) due to adenosine deaminase deficiency is a target for gene therapy.

Purpose of the Study:

• To evaluate the safety and efficacy of gene transfer into hematopoietic cells in patients with adenosine deaminase deficiency.

Main Methods:

• Retrovirus-mediated gene transfer of the human adenosine deaminase gene into patient hematopoietic cells.
• Clinical administration of genetically repaired T-cells, hematopoietic stem cells, or both.

Main Results:

• Successful gene transfer and expression of human adenosine deaminase in vivo in descendants of hematopoietic stem cells in preclinical models.
• Ten patients received gene therapy without any reported side effects.
• Transduced circulating blood cells are detectable in patients, though at lower frequencies compared to preclinical studies without conditioning.

Conclusions:

• Hematopoietic stem cell gene therapy is a viable approach for treating adenosine deaminase deficiency.
• The absence of myeloablation in patient studies may explain lower initial transduction frequencies compared to animal models.