Gene therapy for infantile malignant osteopetrosis: review of pre-clinical research and proof-of-concept for phenotypic reversal

• Main Authors: Ilana Moscatelli, Elena Almarza, Axel Schambach, David Ricks, Ansgar Schulz, Christopher D. Herzog, Kim Henriksen, Maria Askmyr, Jonathan D. Schwartz, Johan Richter
• Format: Article
• Language: English
• Published: Elsevier 2021-03-01
• Series: Molecular Therapy: Methods & Clinical Development
• Subjects: infantile malignant osteopetrosis; lentivirus; gene therapy; autosomal recessive osteopetrosis; hematopoietic stem and progenitor cells; osteoclast disorders
• Online Access: http://www.sciencedirect.com/science/article/pii/S2329050120302576

Infantile malignant osteopetrosis is a devastating disorder of early childhood that is frequently fatal and for which there are only limited therapeutic options. Gene therapy utilizing autologous hematopoietic stem and progenitor cells represents a potentially advantageous therapeutic alternative for this multisystemic disease. Gene therapy can be performed relatively rapidly following diagnosis, will not result in graft versus host disease, and may also have potential for reduced incidences of other transplant-related complications. In this review, we have summarized the past sixteen years of research aimed at developing a gene therapy for infantile malignant osteopetrosis; these efforts have culminated in the first clinical trial employing lentiviral-mediated delivery of TCIRG1 in autologous hematopoietic stem and progenitor cells.