Sickle Cell Disease Fact Sheet
CIRM funds many projects seeking to better understand sickle cell disease and to translate those discoveries into new therapies.
Description
Around 100,000 Americans have sickle cell disease and despite decades of research the average life expectancy has dropped from 42 in 1995 to 39 today. It is a disease that largely targets the African-American community and to a lesser degree the Hispanic community.
Sickle cell disease is a genetic disorder that causes red blood cells to assume a sickle shape under stress, clogging blood vessels and producing episodes of excruciating pain, called crises, and leading to progressive organ damage. By twenty years of age about 15 percent of people with sickle cell disease have had major strokes and by 40 almost half of the patients have significant mental dysfunction.
The most common recommendation for people with sickle cell disease is to stay hydrated. The more water a person drinks, the less likely it is that their abnormal blood cells will clog their blood vessels. Another effective treatment is a medication called hydroxyurea, which reduces crises by 50 percent and death by 40 percent, but most adults are not treated. The populations most effected by sickle cell disease also suffer from significant health care disparities, which lower the quality of care they receive for their disease.
Bone marrow transplants are used to treat children with the most severe cases of the disease. In fact one of CIRM’s former Board members, the late Bert Lubin, MD, the President and CEO of Children’s Hospital and Research Center Oakland, has been a leader in developing this therapy for kids with sickle cell disease (his bio is here). The replacement bone marrow cells generate an entirely new blood system for the patient. However, bone marrow transplants are extremely risky and require a matched sibling donor and even under the best conditions there is always the risk of rejection.
Research funded by California’s stem cell agency focuses on making bone marrow transplants safer and more effective for treating people with sickle cell disease. In one project, the researchers intend to remove bone marrow from the patient and fix the genetic defect in the blood-forming stem cells. Then those cells can be reintroduced into the patient to create a new, healthy blood system. Because the cells come from the patient this technique avoids the issue of rejection. Other researchers are developing ways of making bone marrow transplants safer.
Clinical Stage Programs
University of California, Los Angeles
This team of researchers plans to remove bone marrow cells from people with sickle cell disease and fix the genetic mutation that causes the disease. The team will then reintroduce the new cells into the patient. Those cells will then generate new, healthy blood cells.
City of Hope, Duarte
Scientists at the City of Hope are going to transplant blood-forming stem cells from a donor into a patient who has received a milder, less toxic chemotherapy treatment that removes some but not all of the patient’s diseased bone marrow stem cells. This allows the donor stem cells to engraft and create a healthy supply of non-diseased blood cells without causing an immune reaction in the patient. The hope is that this treatment will cure patients with more severe forms of SCD who aren’t able to benefit from currently available blood stem cell transplants that require the administration of more toxic chemotherapy drugs.
CIRM Grants Targeting Sickle Cell Disease
| Researcher Name | Institution | Grant Title | Grant Type | Award Amount |
| Dr. Camilla Forsberg | University of California, Santa Cruz | Determining how age-specific heterogeneity of human hematopoietic stem cells and megakaryocyte progenitors contribute to thrombotic disease upon aging | Foundation – Discovery Stage Research Projects | $1,336,800 |
| David Williams | Boston Children’s Hospital | Phase 2 Study of Hematopoietic Stem Cell Gene Transfer Inducing Fetal Hemoglobin in Sickle Cell Disease | Cure Sickle Cell Initiative Clinical Trial Stage Projects | $8,333,581 |
| Mark C. Walters M.D. | University of California, San Francisco | Transplantation of CRISPR-CAS9 Corrected Hematopoietic Stem Cells (CRISPR_SCD001) in Patients with Severe Sickle Cell Disease | Cure Sickle Cell Initiative Clinical Trial Stage Projects | $8,389,407 |
| Dr Pierre Caudrelier | ExCellThera Inc. | A Phase 1 Study of ECT-001 Expanded Cord Blood and Myeloablative Regimen with Reduced Toxicity in Patients with Severe Sickle Cell Disease. | Cure Sickle Cell Initiative Clinical Trial Stage Projects | $600,000 |
| Dr. Caroline Y. Kuo | University of California, Los Angeles | Evaluation of Gene Therapy Approaches for Autosomal Recessive Hyper IgE Syndrome Due to Mutations in DOCK8 | Progression Award – Discovery Stage Research Projects | $234,000 |
| Mr. Fyodor Urnov | University of California, Berkeley | A Treatment for Artemis-deficient Severe Combined Immunodeficiency using Non-Viral CRISPR-driven Safe Harbor Transgenesis in Hematopoietic Stem Cells | Quest – Discovery Stage Research Projects | $1,809,372 |
| Dr Michael J Bollong | Scripps Research Institute | Therapeutics to overcome the differentiation roadblock in Myelodysplastic Syndrome (MDS) | Quest – Discovery Stage Research Projects | $1,244,160 |
| Dr. Caroline Y. Kuo | University of California, Los Angeles | Defining the Optimal Gene Therapy Approach of Human Hematopoietic Stem Cells for the Treatment of Dedicator of Cytokinesis 8 (DOCK8) Deficiency | Quest – Discovery Stage Research Projects | $1,386,232 |
| Dr. Donald B. Kohn | University of California, Los Angeles | Hematopoietic Stem Cell Gene Therapy for Alpha Thalassemia | Quest – Discovery Stage Research Projects | $1,177,739 |
| Dr. Judith A Shizuru | Stanford University | Targeted Immunotherapy-Based Blood Stem Cell Transplantation | Quest – Discovery Stage Research Projects | $1,341,910 |
| Kathleen M Sakamoto | Stanford University | Small Molecules to inhibit Nemo-like Kinase for Treatment of Diamond Blackfan Anemia | Quest – Discovery Stage Research Projects | $848,098 |
| Dr. Donald B. Kohn | University of California, Los Angeles | Hematopoietic Stem Cell Gene Therapy for X-linked Agammaglobulinemia | Quest – Discovery Stage Research Projects | $219,230 |
| Dr. Saswati Chatterjee | City of Hope, Beckman Research Institute | Genome Editing of Sinusoidal Endothelial Stem Cells for Permanent Correction of Hemophilia A | Quest – Discovery Stage Research Projects | $2,182,193 |
| Dr. Caroline Y. Kuo | University of California, Los Angeles | Targeted Gene Editing in the Treatment of X-Linked Hyper-IgM Syndrome | Quest – Discovery Stage Research Projects | $1,512,333 |
| Dr. John P Chute | University of California, Los Angeles | Protein tyrosine phosphatase – sigma inhibitors for hematopoietic regeneration | Quest – Discovery Stage Research Projects | $2,115,735 |
| Dr. Rosa Bacchetta | Stanford University | GENE EDITING FOR FOXP3 IN HUMAN HSC | Quest – Discovery Stage Research Projects | $984,228 |
| Professor Hiromitsu Nakauchi | Stanford University | Optimizing self-renewal signaling kinetics to stabilize ex vivo hematopoietic stem cell expansion | Inception – Discovery Stage Research Projects | $210,906 |
| Dr. Tannishtha Reya | University of California, San Diego | Reprogramming human stem cells for blood cell generation | Inception – Discovery Stage Research Projects | $210,060 |
| Dr. Marcus Oliver Muench | Vitalant Research Institute | Modulating Liver Sinusoidal Endothelial Cell Permeability to Enhance Engraftment of Endothelial Cell Progenitors for the Treatment of Hemophilia A | Inception – Discovery Stage Research Projects | $180,000 |
| Dionicio Siegel | University of California, San Diego | New Methods for the Chemical Expansion of Hematopoietic Stem and Progenitor Cells | Inception – Discovery Stage Research Projects | $232,200 |
| Dr. Steven Mack PhD | University of California, San Francisco | Development of a Noninvasive Prenatal Test for Beta-Hemoglobinopathies for Earlier Stem Cell Therapeutic Interventions | Diagnostic Translational Research Projects | $633,014 |
| Dr. Henry A. Erlich Ph.D. | UCSF Benioff Children’s Hospital Oakland | Development of a Noninvasive Prenatal Test for Beta-Hemoglobinopathies for Earlier Stem Cell Therapeutic Interventions | Diagnostic Translational Research Projects | $1,074,177 |
| Luke Riggan | ImmunoVec | Hematopoietic Stem Cell Gene Therapy for Wiskott Aldrich Syndrome | Therapeutic Translational Research Projects | $3,999,899 |
| Luke Riggan | ImmunoVec | Hematopoietic Stem Cell Gene Therapy for IPEX Syndrome | Therapeutic Translational Research Projects | $3,551,332 |
| Dr. Caroline Y. Kuo | University of California, Los Angeles | Ex Vivo Gene Editing of Human Hematopoietic Stem Cells for the Treatment of X-Linked Hyper-IgM Syndrome | Therapeutic Translational Research Projects | $4,896,628 |
| Mark C. Walters M.D. | University of California, San Francisco | Curing Sickle cell Disease with CRISPR-Cas9 genome editing | Therapeutic Translational Research Projects | $60,635 |
| Dr. Mark C. Walters M.D. | UCSF Benioff Children’s Hospital Oakland | Curing Sickle cell Disease with CRISPR-Cas9 genome editing | Therapeutic Translational Research Projects | $4,394,276 |
| Dr. Christel H. Uittenbogaart | Midwinter Conference of Immunologists | 62nd Midwinter Conference of Immunologists | Conference II | $49,325 |
| Dr. Everett H. Meyer | Stanford University | Cellular Immune Tolerance Symposium | Conference II | $31,225 |
| Dr. Naynesh R. Kamani | American Association of Blood Banks | 15th International Cord Blood Sympsium | Conference II | $30,000 |
| Dr. Naynesh R. Kamani | American Association of Blood Banks | 14th International Cord Blood Symposium: Give Life Twice | Conference II | $15,000 |
| Dr. Joseph C. Wu | Stanford University | Drug Discovery & Stem Cell Models for Cardiovascular Disease Conference | Conference II | $7,500 |
| Dr. David Traver | International Society for Experimental Hematology | International Society for Experimental Hematology, 45th Annual Scientific Meeting | Conference II | $25,000 |
| Dr. Matthew H Porteus | Stanford University | Reduced intensity conditioning with JSP191 prior to TCRαβ+ T-cell/CD19+ B-cell depleted hematopoietic stem cell transplant for Fanconi Anemia patients | Clinical Trial Stage Projects | $10,642,420 |
| Ryotaro Nakamura | City of Hope, Beckman Research Institute | Treatment of Severe Aplastic Anemia by induction of mixed chimerism using CD4+ T cell depleted haploidentical donor stem cell transplant | Clinical Trial Stage Projects | $9,054,216 |
| Alice Bertaina | Stanford University | Sequential same donor αβdepleted-HSCT from an HLA-partially matched donor allowing immunosuppression free kidney transplant | Clinical Trial Stage Projects | $11,998,188 |
| Dr. Rosa Bacchetta | Stanford University | Phase 1 Study of Autologous CD4LVFOXP3 in Participants with IPEX Syndrome | Clinical Trial Stage Projects | $11,999,179 |
| Dr. Kinnari Patel | Rocket Pharmaceuticals, Inc. | LADICell | Clinical Trial Stage Projects | $5,867,085 |
| Wendy Pang | Jasper Therapeutics, Inc. | A monoclonal antibody that depletes blood stem cells and enables chemotherapy free transplants | Clinical Trial Stage Projects | $2,313,398 |
| Dr. Judith A Shizuru | Stanford University | A monoclonal antibody that depletes blood stem cells and enables chemotherapy free transplants | Clinical Trial Stage Projects | $1,113,487 |
| Bettina Cockroft | Sangamo BioSciences, Inc. | A Phase 1/2 Study to Assess the Safety, Tolerability, and Efficacy of ST-400 Autologous HSPC Transplant in Transfusion-dependent β-Thalassemia | Clinical Trial Stage Projects | $5,150,000 |
| Dr. De-Fu Zeng | City of Hope, Beckman Research Institute | Treatment of sickle cell disease by induction of mixed chimerism and immune tolerance using CD4+ T-depleted haploidentical blood stem cell transplant | Clinical Trial Stage Projects | $4,352,180 |
| Mort Cowan | University of California, San Francisco | Gene Transfer for Artemis-Deficient Severe Combined Immunodeficiency Using a Lentiviral Vector to Transduce Autologous CD34 Hematopoietic Stem Cells | Clinical Trial Stage Projects | $12,000,000 |
| Michael A. Pulsipher | Children’s Hospital of Los Angeles | Antiviral Cellular Therapy for Enhancing T-cell Reconstitution Before or After Hematopoietic Stem Cell Transplantation (ACES) | Clinical Trial Stage Projects | $4,825,587 |
| Stephen Gottschalk | 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 |
| Dr. Donald B. 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 | $5,827,000 |
| Leslie Meltzer | Orchard Therapeutics plc | 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 | $2,638,745 |
| Dr. Donald B 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 | $10,156,925 |
| Dr. Tippi C. Mackenzie MD | University of California, San Francisco | In Utero Hematopoietic Stem Cell Transplantation For The Treatment Of Fetuses With Alpha Thalassemia Major | Clinical Trial Stage Projects | $10,906,978 |
| Dr. Donald B. 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 |
| Dr. Ryan L. Wong | ImmunoVec | Hematopoietic Stem Cell Gene Therapy for XCGD | Late Stage Preclinical Projects | $3,999,959 |
| Dr. Rosa Bacchetta | Stanford University | IND-enabling activities for a Phase 1 Study of Autologous CD4LVFOXP3 T Cells in Subjects with IPEX Syndrome | Late Stage Preclinical Projects | $5,002,496 |
| Mark C. Walters M.D. | University of California, San Francisco | Curing Sickle cell Disease with CRISPR-Cas9 genome editing | Late Stage Preclinical Projects | $2,242,805 |
| Dr. Matthew H Porteus | Stanford University | Genome Editing of Autologous Hematopoietic Stem Cells to Treat Sickle Cell Disease | Late Stage Preclinical Projects | $4,849,363 |
| Dr Jennifer M 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 |
| Dr. Matthew H Porteus | Stanford University | Pre-clinical development of gene correction therapy of hematopoietic stem cells for SCID-X1 | Preclinical Development Awards | $874,877 |
| Dr. Hanna Mikkola | University of California, Los Angeles | A suite of engineered human pluripotent stem cell lines to facilitate the generation of hematopoietic stem cells | Tools and Technologies III | $1,382,400 |
| Dr. Andrew D. Leavitt MD | University of California, San Francisco | Small molecule tools and scale-up technologies to expand human umbilical cord blood stem and progenitor cells for clinical and research use | Tools and Technologies III | $1,416,600 |
| Dr. Irving L Weissman MD | Stanford University | Identification and isolation of transplantable human hematopoietic stem cells from pluripotent cell lines; two steps from primitive hematopoiesis to transplantable definitive cells, and non-toxic conditioning of hosts for hematopoeitic stem cell transp… | Tools and Technologies III | $1,271,952 |
| Dr. Alice F Tarantal | University of California, Davis | 9th Annual Gene Therapy Symposium for Heart, Lung and Blood Diseases | Conference | $12,000 |
| Dr. Alice F Tarantal | University of California, Davis | 10th Annual Gene Therapy Symposium for Heart, Lung, and Blood Diseases | Conference | $18,300 |
| Dr. Alice F Tarantal | University of California, Davis | 11th Annual Gene Therapy Symposium for Heart, Lung, and Blood Diseases | Conference | $16,850 |
| Dr. Brian Black | University of California, San Francisco | Weinstein Cardiovascular Development Conference | Conference | $35,000 |
| Dr. Donald B. Kohn | Children’s Hospital of Los Angeles | STEM CELL GENE THERAPY FOR SICKLE CELL DISEASE | Disease Team Planning | $12,131 |
| Dr. Dianne McKay | University of California, San Diego | Role of intracytoplasmic pattern recognition receptors in HSC engraftment | Basic Biology V | $615,639 |
| Dr. Lili Yang | University of California, Los Angeles | Differentiation of Human Hematopoietic Stem Cells into iNKT Cells | Basic Biology V | $614,400 |
| Dr. Donald B. Kohn | University of California, Los Angeles | Clinical Trial of Stem Cell Gene Therapy for Sickle Cell Disease | Disease Team Therapy Development III | $13,145,465 |
| Dr. Fyodor D Urnov | Sangamo BioSciences, Inc. | A Treatment For Beta-thalassemia via High-Efficiency Targeted Genome Editing of Hematopoietic Stem Cells | Strategic Partnership II | $2,760,540 |
| Dr. Donald B. Kohn | University of California, Los Angeles | Beta-Globin Gene Correction of Sickle Cell Disease in Hematopoietic Stem Cells | Early Translational IV | $1,651,884 |
| Dr. Inder M. Verma | Salk Institute for Biological Studies | Development of a cell and gene based therapy for hemophilia | Early Translational IV | $2,298,634 |
| David M. Davidson | Bluebird Bio | A Phase 1/2, Open Label Study Evaluating the Safety and Efficacy of Gene Therapy in Subjects with β-Thalassemia by Transplantation of Autologous Hematopoietic Stem Cells Transduced with the Lentiviral Vector LentiGlobin® Encoding the Human β-A-T87Q-… | Strategic Partnership I | $0 |
| Dr. Tippi C. Mackenzie MD | University of California, San Francisco | In Utero Embryonic Stem Cell Transplantation to Treat Congenital Anomalies | New Faculty Physician Scientist | $2,661,742 |
| Ann Capela Zovein | University of California, San Francisco | Human endothelial reprogramming for hematopoietic stem cell therapy. | New Faculty Physician Scientist | $2,197,683 |
| Dr. Judith A Shizuru | Stanford University | A monoclonal antibody that depletes blood stem cells and enables chemotherapy free transplants | Disease Team Therapy Development – Research | $18,990,683 |
| Dr. Gay Miriam Crooks | University of California, Los Angeles | Forming the Hematopoietic Niche from Human Pluripotent Stem Cells | Basic Biology III | $1,252,857 |
| Dr. Irving L Weissman MD | Stanford University | Antibody tools to deplete or isolate teratogenic, cardiac, and blood stem cells from hESCs | Tools and Technologies II | $1,463,814 |
| Dr. John P Chute | University of California, Los Angeles | Niche-Focused Research: Discovery & Development of Hematopoietic Regenerative Factors | Research Leadership | $4,645,297 |
| Professor Hiromitsu Nakauchi | Stanford University | Generation of functional cells and organs from iPSCs | Research Leadership | $5,426,135 |
| Dr. Hanna Mikkola | University of California, Los Angeles | Mechanisms of Hematopoietic stem cell Specification and Self-Renewal | New Faculty I | $2,286,900 |
| Dr. Inder M. Verma | Salk Institute for Biological Studies | Curing Hematological Diseases | Early Translational I | $5,979,252 |
| Dr. Nicholas R.J. Gascoigne | Scripps Research Institute | Role of Innate Immunity in hematopoeitic stem cell-mediated allograft tolerance | Transplantation Immunology | $1,705,554 |
| Dr. David H Raulet | University of California, Berkeley | Inactivating NK cell reactivity to facilitate transplantation of stem cell derived tissue | Transplantation Immunology | $952,896 |
| Dr. Tippi C. Mackenzie MD | University of California, San Francisco | Maternal and Fetal Immune Responses to In Utero Hematopoietic Stem Cell Transplantation | Transplantation Immunology | $1,230,869 |
| Dr. Judith A Shizuru | Stanford University | Purified allogeneic hematopoietic stem cells as a platform for tolerance induction | Transplantation Immunology | $1,233,275 |
| Dr. Fred H. Gage | Salk Institute for Biological Studies | Development of Induced Pluripotent Stem Cells for Modeling Human Disease | New Cell Lines | $1,737,720 |
| Dr. Irving L Weissman MD | Stanford University | Prospective isolation of hESC-derived hematopoietic and cardiomyocyte stem cells | Comprehensive Grant | $2,471,386 |
| Dr. Hanna Mikkola | University of California, Los Angeles | Improving microenvironments to promote hematopoietic stem cell development from human embryonic stem cells | SEED Grant | $550,241 |
| Dr. Cornelis Murre | University of California, San Diego | Generation of long-term cultures of human hematopoietic multipotent progenitors from embryonic stem cells | SEED Grant | $473,952 |
| Dr. Steven Edward Artandi | Stanford University | Self-renewal and senescence in iPS cells derived from patients with a stem cell disease | Basic Biology II | $931,285 |
| Dr. Donald B. Kohn | University of California, Los Angeles | Stem Cell Gene Therapy for Sickle Cell Disease | Disease Team Research I | $8,833,695 |
| Dr. Luisa Iruela-Arispe | University of California, Los Angeles | Molecular Characterization and Functional Exploration of Hemogenic Endothelium | Basic Biology I | $1,371,477 |
| | | | Total:
$294,056,599.60 |
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