Using targeted immunosuppression, bone marrow transplant, and gene repair to cure IPEX syndrome and other immune dysregulation syndromes

Technology Overview

Immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome is a rare disorder that presents with severe autoimmunity and is linked to specific mutations of the FOXP3 transcription factor. To date, more than 55 gene mutations in FOXP3 have been reported to be associated with IPEX. FOXP3 is primarily expressed in regulatory T cells, which play a primary role in the control of immune responses. Consequently, mutations in FOXP3 can lead to unchecked autoimmune responses and subsequent inflammation affecting multiple organs.

Dr. Troy Torgerson

The Torgerson lab is investigating the molecular basis of IPEX and other immune dysregulation syndromes, with the goal of linking clinical phenotypes to genetic genotypes. While many IPEX patients harbor FOXP3 mutations, a substantial subset of patients present with the clinical phenotype of IPEX but lack alterations in FOXP3. Additionally, depending on the specific mutation in FOXP3, clinical disease presentation can vary widely in IPEX patients. Once the phenotype-genotype link has been defined, it may be possible to predict clinical outcome based on the presence of specific mutations, and to develop targeted therapeutics for these rare, but well characterized, patient populations.

Utilizing a variety of approaches to study the mutations found in patients, the Torgerson lab is characterizing the basic biology of IPEX and other immunodeficiencies and autoimmune disorders, and generating clinically relevant models for testing potential new therapeutics. Currently, hematopoietic stem cell transplantation remains the only known cure for IPEX. However, recent work in the Torgerson lab has focused on developing gene repair approaches as potential cures for IPEX and for X-linked Hyper IgM syndrome. This research, being performed in human cells and using humanized mouse models, is generating promising preclinical data that will hopefully translate into cures for these disorders.

Stage of Development

  • Pre-clinical in vitro
  • Pre-clinical in vivo

Partnering Opportunities

  • Collaborative research opportunity
  • Sponsored research agreement
  • Consultation agreement
  • Animal models for IPEX and other immune dysregulation syndromes
  • Sample access

Publications

  1. Hubbard N, Hagin D, Sommer K, Song Y, Khan I, Clough C, Ochs H, Rawlings D, Scharenberg A, Torgerson T. Targeted gene editing restores regulated CD40L expression and function in X-HIGM T cells. Blood. 2016.
  2. Burroughs L, Nemecek E, Torgerson T, et al. Treosulfan-Based Conditioning and Hematopoietic Cell Transplantation for Nonmalignant Diseases: A Prospective Multicenter Trial. Biology of Blood and Marrow Transplantation. 2014;20(12):1996-2003.
  3. Burtner C, Beard B, Kennedy D, Wohlfahrt M, Adair J, Trobridge G, Scharenberg A, Torgerson T, et al. Intravenous injection of a foamy virus vector to correct canine SCID-X1. Blood. 2014;123(23):3578-3584.

Learn More

To learn more about partnering with Seattle Children’s Research Institute on this or other projects, please contact:

Dr. Elizabeth Aylward
Director, Office of Science-Industry Partnerships
Email
206-844-1065