Towards gene therapy for IPEX syndrome

Eur J Immunol. 2022 May;52(5):705-716. doi: 10.1002/eji.202149210. Epub 2022 Apr 13.

Abstract

Immune dysregulation polyendocrinopathy enteropathy X linked (IPEX) syndrome is an uncurable disease of the immune system, with immune dysregulation that is caused by mutations in FOXP3. Current treatment options, such as pharmacological immune suppression and allogeneic hematopoietic stem cell transplantation, have been beneficial but present limitations, and their life-long consequences are ill-defined. Other similar blood monogenic diseases have been successfully treated using gene transfer in autologous patient cells, thus providing an effective and less invasive therapeutic. Development of gene therapy for patients with IPEX is particularly challenging because successful strategies must restore the complex expression profile of the transcription factor FOXP3, ensuring it is tightly regulated and its cell subset-specific roles are maintained. This review summarizes current efforts toward achieving gene therapy to treat immune dysregulation in IPEX patients.

Keywords: DNA editing; FOXP3; Gene therapy; IPEX; Treg cells.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 1* / congenital
  • Diarrhea
  • Forkhead Transcription Factors / genetics
  • Genetic Diseases, X-Linked* / genetics
  • Genetic Diseases, X-Linked* / therapy
  • Genetic Therapy
  • Humans
  • Immune System Diseases* / congenital
  • Immune System Diseases* / genetics
  • Immune System Diseases* / therapy
  • Mutation
  • T-Lymphocytes, Regulatory

Substances

  • Forkhead Transcription Factors

Supplementary concepts

  • Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome