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

Research output: Contribution to journalReview articlepeer-review

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. Infantile malignant osteopetrosis (IMO) presents a highly unmet medical need with limited therapeutic options. Gene therapy utilizing autologous hematopoietic stem and progenitor cells represents a potentially advantageous therapeutic alternative for this disease. Here, we have summarized all nonclinical studies supporting the initiation of a clinical gene therapy trial for IMO.

Original languageEnglish
Pages (from-to)389-397
Number of pages9
JournalMolecular Therapy - Methods and Clinical Development
Volume20
DOIs
Publication statusPublished - 2021

Subject classification (UKÄ)

  • Medical Genetics and Genomics (including Gene Therapy)
  • Orthopaedics

Free keywords

  • autosomal recessive osteopetrosis
  • gene therapy
  • hematopoietic stem and progenitor cells
  • infantile malignant osteopetrosis
  • lentivirus
  • osteoclast disorders

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