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

Ilana Moscatelli; Elena Almarza; Axel Schambach; David Ricks; Ansgar Schulz; Christopher D Herzog; Kim Henriksen; Maria Askmyr; Jonathan D Schwartz; Johan Richter

doi:10.1016/j.omtm.2020.12.009

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

Mol Ther Methods Clin Dev. 2020 Dec 25:20:389-397. doi: 10.1016/j.omtm.2020.12.009. eCollection 2021 Mar 12.

Authors

Affiliations

¹ Department of Molecular Medicine and Gene Therapy, Lund Strategic Center for Stem Cell Biology, Lund University, Lund, Sweden.
² Rocket Pharmaceuticals, Inc., New York, NY, USA.
³ Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.
⁴ Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Germany.
⁶ Nordic Bioscience A/S, Herlev, Denmark.

Abstract

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.

Keywords: autosomal recessive osteopetrosis; gene therapy; hematopoietic stem and progenitor cells; infantile malignant osteopetrosis; lentivirus; osteoclast disorders.

Publication types

Review