SCID and Primary Immunodeficiency Fact Sheet

CIRM funds many projects seeking to better understand Severe Combined Immune Deficiency (SCID) and other primary immunodeficiency diseases to translate those discoveries into new therapies.

Description

Primary immunodeficiencies are disease that compromise or destroy the immune system, leaving patients susceptible to serious infections. Typically, these diseases have genetic causes and many of them are rare. Severe combined immune deficiency or SCID is an example of a primary immunodeficiency.

SCID – also known as ‘bubble boy disease’ - is a rare genetic disorder, effecting one in 30,000 newborns. Left untreated the children die before the age of 2, and the only readily available treatment involves high-risk bone marrow transplants. Because these patients already have a compromised immune system, 10 to 20 percent don’t survive the transplant.

Gene therapy has been used to correct the defect in certain types of SCID, but early gene modifying techniques resulted in some patients developing cancer. Newer gene therapy techniques appear to be safer but have been tried on fewer than 20 patients.

Researchers funded by California’s stem cell agency are looking for a better alternative to help these children. They are trying to improve the safety of bone marrow transplant (BMT), which essentially uses the stem cells in bone marrow to give the children a new immune system that works properly. Most of the risk of current BMT procedures comes from the radiation or chemotherapy given to patients before the transplant to wipe out the patient’s own stem cells that form immune cells. These regimens kill many types of cells beyond those intended and result in numerous toxic side effects.

Clinical Stage Programs

Stanford School of Medicine (X-linked SCID)

This team proposes to replace SCID patients’ dysfunctional immune cells with healthy ones using a safer form of bone marrow transplant (BMT). They plan to eliminate the bad cells with an antibody, a protein, that very specifically targets and eliminates blood forming stem cells. If successful, the procedure could open up similar BMT therapies to patients with other auto-immune diseases such as multiple sclerosis, lupus or diabetes that are generally not candidates for BMT currently. These diseases, while debilitating, are not immediately life-threatening and generally don’t warrant the risks involved in BMT the way it is done today.

St. Jude Children's Research Hospital

The team is using gene therapy to correct a genetic mutation in the blood stem cells of patients with X-linked SCID. The corrected stem cells are then transplanted back into the patient to restore their immune system's ability to produce healthy immune cells. This will allow the patient to fight off infections and will hopefully cure their disease. 

University of California, Los Angeles (Chronic granulomatous disease and ADA-SCID)

The team is developing a therapy for chronic granulomatous disease: a very rare primary immune deficiency disease that results in severe and recurrent infections that can impact quality and length of life. The UCLA team uses the patient’s own genetically modified blood stem cells to create a new blood supply and immune system to eradicate the problem.

UCLA is also developing a therapy for a form of SCID called adenosine deaminase (ADA)-deficient SCID. Patients with ADA-SCID lack an important enzyme called adenosine deaminase in their immune cells. Without this enzyme, toxic by-products build up in their immune cells and eventually kill them off leaving the patient susceptible to deadly infections. The group from UCLA will genetically modify patient blood stem cells to remove the disease-causing mutation and transplant these corrected stem cells back into the patient to create a new, healthy immune system. 

CIRM Grants Targeting Immune Diseases including SCID

Researcher name Institution Grant Title Grant Type Approved funds
Thomas Lane University of California, Irvine Human Embryonic Stem Cells and Remyelination in a Viral Model of Demyelination SEED Grant $368,081
Yang Xu University of California, San Diego Induction of immune tolerance to human embryonic stem cell-derived allografts Transplantation Immunology $1,192,680
Kenneth Weinberg Stanford University Embryonic stem cell-derived thymic epithelial cells SEED Grant $628,793
Judith Shizuru Stanford University A monoclonal antibody that depletes blood stem cells and enables chemotherapy free transplants Disease Team Therapy Planning I $90,147
Irving Weissman Stanford University Prospective isolation of hESC-derived hematopoietic and cardiomyocyte stem cells Comprehensive Grant $2,471,386
Morton Cowan University of California, San Francisco Gene Correction of Autologous Hematopoietic Stem Cells in Artemis Deficient SCID Early Translational III $3,931,662
Samuel Pleasure University of California, San Francisco Human stem cell derived oligodendrocytes for treatment of stroke and MS Comprehensive Grant $2,459,235
Judith Shizuru Stanford University A monoclonal antibody that depletes blood stem cells and enables chemotherapy free transplants Disease Team Therapy Development - Research $19,068,382
Zack Jerome University of California, Los Angeles Human Embryonic Stem Cell Therapeutic Strategies to Target HIV Disease Comprehensive Grant $2,401,903
Mark Anderson University of California, San Francisco Generation of a functional thymus to induce immune tolerance to stem cell derivatives Basic Biology V $1,191,000
Inder Verma Salk Institute for Biological Studies Curing Hematological Diseases Early Translational I $5,979,252
John Adams University of California, Los Angeles UCLA-UCI Alpha Stem Cell Clinic (ASCC) Consortium Alpha Stem Cell Clinics $8,000,000
Mark Anderson University of California, San Francisco Stem cell differentiation to thymic epithelium for inducing tolerance to stem cells Transplantation Immunology $1,314,089
Matthew Porteus Stanford University Pre-clinical development of gene correction therapy of hematopoietic stem cells for SCID-X1 Preclinical Development Awards $874,877
Jeffrey Bluestone University of California, San Francisco Stem cell tolerance through the use of engineered antigen-specific regulatory T cells Transplantation Immunology $1,152,768
Donald Kohn University of California, Los Angeles A Phase I/II, Non Randomized, Multicenter, Open-Label Study of G1XCGD (Lentiviral Vector Transduced CD34+ Cells) in Patients With X-Linked Chronic Granulomatous Disease Clinical Trial Stage Projects $7,083,364
Gay Crooks University of California, Los Angeles Engineering Thymic Regeneration to Induce Tolerance Transplantation Immunology $1,235,445
Donald Kohn University of California, Los Angeles Primary Immune Deficiency Treatment Consortium (PIDTC) Annual Scientific Workshop Conference II $29,807
Husein Hadeiba Palo Alto Institute for Research and Education Application of Tolerogenic Dendritic Cells for Hematopoietic Stem Cell Transplantation Transplantation Immunology $733,061
Jennifer Puck University of California, San Francisco Ex Vivo Transduction of the Human Artemis (DCLRE1C) cDNA by Lentiviral Vector AProArt into CD34+ Hematopoietic Cells for Artemis (ART)-Deficient Severe Combined Immunodeficiency (SCID) Late Stage Preclinical Projects $4,268,865
Jeanne Loring Scripps Research Institute Thymus based tolerance to stem cell therapies Transplantation Immunology $1,108,921
Donald Kohn University of California, Los Angeles Efficacy and safety of cryopreserved autologous CD34+ HSC transduced with EFS lentiviral vector encoding for human ADA gene in ADA-SCID subjects Clinical Trial Stage Projects $19,065,745
David DiGiusto City of Hope Development of RNA-based approaches to stem cell gene therapy for HIV Early Translational II $3,097,160
Tippi MacKenzie University of California, San Francisco Maternal and Fetal Immune Responses to In Utero Hematopoietic Stem Cell Transplantation Transplantation Immunology $1,230,869
Rosa Bacchetta Stanford University GENE EDITING FOR FOXP3 IN HUMAN HSC Quest - Discovery Stage Research Projects $984,228
John Zaia City of Hope ZINC FINGER NUCLEASE-BASED STEM CELL THERAPY FOR AIDS Disease Team Research I $14,536,969
Anjana Rao La Jolla Institute for Allergy and Immunology Generation of regulatory T cells by reprogramming Transplantation Immunology $1,464,446
Brian Sorrentino St. Jude Children's Research Hospital Lentiviral Gene Therapy for Infants with X-linked Severe Combined Immunodeficiency using Autologous Bone Marrow Stem Cells and Busulfan Conditioning Clinical Trial Stage Projects $11,924,780
Irvin Chen University of California, Los Angeles HPSC based therapy for HIV disease using RNAi to CCR5. Disease Team Research I $9,905,604
Ellen Robey University of California, Berkeley Human Immune System Mouse models as preclinical platforms for stem cell derived grafts Transplantation Immunology $1,005,605
Michele Calos Stanford University Safe, efficient creation of human induced pluripotent stem cells without the use of retroviruses New Cell Lines $1,406,875
Judith Shizuru Stanford University Purified allogeneic hematopoietic stem cells as a platform for tolerance induction Transplantation Immunology $1,233,275
Irvin Chen University of California, Los Angeles Genetic modification of the human genome to resist HIV-1 infection and/or disease progression SEED Grant $616,800
Kenneth Weinberg Stanford University Engineered immune tolerance by Stem Cell-derived thymic regeneration Transplantation Immunology $1,271,729
Total:
$133,327,803.00

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