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 NameInstitutionGrant TitleGrant TypeAward Amount
Dr. Camilla ForsbergUniversity of California, Santa CruzDetermining how age-specific heterogeneity of human hematopoietic stem cells and megakaryocyte progenitors contribute to thrombotic disease upon agingFoundation – Discovery Stage Research Projects$1,336,800
David WilliamsBoston Children’s HospitalPhase 2 Study of Hematopoietic Stem Cell Gene Transfer Inducing Fetal Hemoglobin in Sickle Cell DiseaseCure Sickle Cell Initiative Clinical Trial Stage Projects$8,333,581
Mark C. Walters M.D.University of California, San FranciscoTransplantation of CRISPR-CAS9 Corrected Hematopoietic Stem Cells (CRISPR_SCD001) in Patients with Severe Sickle Cell DiseaseCure Sickle Cell Initiative Clinical Trial Stage Projects$8,389,407
Dr Pierre CaudrelierExCellThera 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. KuoUniversity of California, Los AngelesEvaluation of Gene Therapy Approaches for Autosomal Recessive Hyper IgE Syndrome Due to Mutations in DOCK8Progression Award – Discovery Stage Research Projects$234,000
Mr. Fyodor UrnovUniversity of California, BerkeleyA Treatment for Artemis-deficient Severe Combined Immunodeficiency using Non-Viral CRISPR-driven Safe Harbor Transgenesis in Hematopoietic Stem CellsQuest – Discovery Stage Research Projects$1,809,372
Dr Michael J BollongScripps Research InstituteTherapeutics to overcome the differentiation roadblock in Myelodysplastic Syndrome (MDS)Quest – Discovery Stage Research Projects$1,244,160
Dr. Caroline Y. KuoUniversity of California, Los AngelesDefining the Optimal Gene Therapy Approach of Human Hematopoietic Stem Cells for the Treatment of Dedicator of Cytokinesis 8 (DOCK8) DeficiencyQuest – Discovery Stage Research Projects$1,386,232
Dr. Donald B. KohnUniversity of California, Los AngelesHematopoietic Stem Cell Gene Therapy for Alpha ThalassemiaQuest – Discovery Stage Research Projects$1,177,739
Dr. Judith A ShizuruStanford UniversityTargeted Immunotherapy-Based Blood Stem Cell TransplantationQuest – Discovery Stage Research Projects$1,341,910
Kathleen M SakamotoStanford UniversitySmall Molecules to inhibit Nemo-like Kinase for Treatment of Diamond Blackfan AnemiaQuest – Discovery Stage Research Projects$848,098
Dr. Donald B. KohnUniversity of California, Los AngelesHematopoietic Stem Cell Gene Therapy for X-linked AgammaglobulinemiaQuest – Discovery Stage Research Projects$219,230
Dr. Saswati ChatterjeeCity of Hope, Beckman Research InstituteGenome Editing of Sinusoidal Endothelial Stem Cells for Permanent Correction of Hemophilia AQuest – Discovery Stage Research Projects$2,182,193
Dr. Caroline Y. KuoUniversity of California, Los AngelesTargeted Gene Editing in the Treatment of X-Linked Hyper-IgM SyndromeQuest – Discovery Stage Research Projects$1,512,333
Dr. John P ChuteUniversity of California, Los AngelesProtein tyrosine phosphatase – sigma inhibitors for hematopoietic regenerationQuest – Discovery Stage Research Projects$2,115,735
Dr. Rosa BacchettaStanford UniversityGENE EDITING FOR FOXP3 IN HUMAN HSCQuest – Discovery Stage Research Projects$984,228
Professor Hiromitsu NakauchiStanford UniversityOptimizing self-renewal signaling kinetics to stabilize ex vivo hematopoietic stem cell expansionInception – Discovery Stage Research Projects$210,906
Dr. Tannishtha ReyaUniversity of California, San DiegoReprogramming human stem cells for blood cell generationInception – Discovery Stage Research Projects$210,060
Dr. Marcus Oliver MuenchVitalant Research InstituteModulating Liver Sinusoidal Endothelial Cell Permeability to Enhance Engraftment of Endothelial Cell Progenitors for the Treatment of Hemophilia AInception – Discovery Stage Research Projects$180,000
Dionicio SiegelUniversity of California, San DiegoNew Methods for the Chemical Expansion of Hematopoietic Stem and Progenitor CellsInception – Discovery Stage Research Projects$232,200
Dr. Steven Mack PhDUniversity of California, San FranciscoDevelopment of a Noninvasive Prenatal Test for Beta-Hemoglobinopathies for Earlier Stem Cell Therapeutic InterventionsDiagnostic Translational Research Projects$633,014
Dr. Henry A. Erlich Ph.D.UCSF Benioff Children’s Hospital OaklandDevelopment of a Noninvasive Prenatal Test for Beta-Hemoglobinopathies for Earlier Stem Cell Therapeutic InterventionsDiagnostic Translational Research Projects$1,074,177
Luke RigganImmunoVecHematopoietic Stem Cell Gene Therapy for Wiskott Aldrich SyndromeTherapeutic Translational Research Projects$3,999,899
Luke RigganImmunoVecHematopoietic Stem Cell Gene Therapy for IPEX SyndromeTherapeutic Translational Research Projects$3,551,332
Dr. Caroline Y. KuoUniversity of California, Los AngelesEx Vivo Gene Editing of Human Hematopoietic Stem Cells for the Treatment of X-Linked Hyper-IgM SyndromeTherapeutic Translational Research Projects$4,896,628
Mark C. Walters M.D.University of California, San FranciscoCuring Sickle cell Disease with CRISPR-Cas9 genome editingTherapeutic Translational Research Projects$60,635
Dr. Mark C. Walters M.D.UCSF Benioff Children’s Hospital OaklandCuring Sickle cell Disease with CRISPR-Cas9 genome editingTherapeutic Translational Research Projects$4,394,276
Dr. Christel H. UittenbogaartMidwinter Conference of Immunologists62nd Midwinter Conference of ImmunologistsConference II$49,325
Dr. Everett H. MeyerStanford UniversityCellular Immune Tolerance SymposiumConference II$31,225
Dr. Naynesh R. KamaniAmerican Association of Blood Banks15th International Cord Blood SympsiumConference II$30,000
Dr. Naynesh R. KamaniAmerican Association of Blood Banks14th International Cord Blood Symposium: Give Life TwiceConference II$15,000
Dr. Joseph C. WuStanford UniversityDrug Discovery & Stem Cell Models for Cardiovascular Disease ConferenceConference II$7,500
Dr. David TraverInternational Society for Experimental HematologyInternational Society for Experimental Hematology, 45th Annual Scientific MeetingConference II$25,000
Dr. Matthew H PorteusStanford UniversityReduced intensity conditioning with JSP191 prior to TCRαβ+ T-cell/CD19+ B-cell depleted hematopoietic stem cell transplant for Fanconi Anemia patientsClinical Trial Stage Projects$10,642,420
Ryotaro NakamuraCity of Hope, Beckman Research InstituteTreatment of Severe Aplastic Anemia by induction of mixed chimerism using CD4+ T cell depleted haploidentical donor stem cell transplantClinical Trial Stage Projects$9,054,216
Alice BertainaStanford UniversitySequential same donor αβdepleted-HSCT from an HLA-partially matched donor allowing immunosuppression free kidney transplantClinical Trial Stage Projects$11,998,188
Dr. Rosa BacchettaStanford UniversityPhase 1 Study of Autologous CD4LVFOXP3 in Participants with IPEX SyndromeClinical Trial Stage Projects$11,999,179
Dr. Kinnari PatelRocket Pharmaceuticals, Inc.LADICellClinical Trial Stage Projects$5,867,085
Wendy PangJasper Therapeutics, Inc.A monoclonal antibody that depletes blood stem cells and enables chemotherapy free transplantsClinical Trial Stage Projects$2,313,398
Dr. Judith A ShizuruStanford UniversityA monoclonal antibody that depletes blood stem cells and enables chemotherapy free transplantsClinical Trial Stage Projects$1,113,487
Bettina CockroftSangamo BioSciences, Inc.A Phase 1/2 Study to Assess the Safety, Tolerability, and Efficacy of ST-400 Autologous HSPC Transplant in Transfusion-dependent β-ThalassemiaClinical Trial Stage Projects$5,150,000
Dr. De-Fu ZengCity of Hope, Beckman Research InstituteTreatment of sickle cell disease by induction of mixed chimerism and immune tolerance using CD4+ T-depleted haploidentical blood stem cell transplantClinical Trial Stage Projects$4,352,180
Mort CowanUniversity of California, San FranciscoGene Transfer for Artemis-Deficient Severe Combined Immunodeficiency Using a Lentiviral Vector to Transduce Autologous CD34 Hematopoietic Stem CellsClinical Trial Stage Projects$12,000,000
Michael A. PulsipherChildren’s Hospital of Los AngelesAntiviral Cellular Therapy for Enhancing T-cell Reconstitution Before or After Hematopoietic Stem Cell Transplantation (ACES)Clinical Trial Stage Projects$4,825,587
Stephen GottschalkSt. Jude Children’s Research HospitalLentiviral Gene Therapy for Infants with X-linked Severe Combined Immunodeficiency using Autologous Bone Marrow Stem Cells and Busulfan ConditioningClinical Trial Stage Projects$11,924,780
Dr. Donald B. KohnUniversity of California, Los AngelesEfficacy and safety of cryopreserved autologous CD34+ HSC transduced with EFS lentiviral vector encoding for human ADA gene in ADA-SCID subjectsClinical Trial Stage Projects$5,827,000
Leslie MeltzerOrchard Therapeutics plcEfficacy and safety of cryopreserved autologous CD34+ HSC transduced with EFS lentiviral vector encoding for human ADA gene in ADA-SCID subjectsClinical Trial Stage Projects$2,638,745
Dr. Donald B KohnUniversity of California, Los AngelesEfficacy and safety of cryopreserved autologous CD34+ HSC transduced with EFS lentiviral vector encoding for human ADA gene in ADA-SCID subjectsClinical Trial Stage Projects$10,156,925
Dr. Tippi C. Mackenzie MDUniversity of California, San FranciscoIn Utero Hematopoietic Stem Cell Transplantation For The Treatment Of Fetuses With Alpha Thalassemia MajorClinical Trial Stage Projects$10,906,978
Dr. Donald B. KohnUniversity of California, Los AngelesA Phase I/II, Non Randomized, Multicenter, Open-Label Study of G1XCGD (Lentiviral Vector Transduced CD34+ Cells) in Patients With X-Linked Chronic Granulomatous DiseaseClinical Trial Stage Projects$7,083,364
Dr. Ryan L. WongImmunoVecHematopoietic Stem Cell Gene Therapy for XCGDLate Stage Preclinical Projects$3,999,959
Dr. Rosa BacchettaStanford UniversityIND-enabling activities for a Phase 1 Study of Autologous CD4LVFOXP3 T Cells in Subjects with IPEX SyndromeLate Stage Preclinical Projects$5,002,496
Mark C. Walters M.D.University of California, San FranciscoCuring Sickle cell Disease with CRISPR-Cas9 genome editingLate Stage Preclinical Projects$2,242,805
Dr. Matthew H PorteusStanford UniversityGenome Editing of Autologous Hematopoietic Stem Cells to Treat Sickle Cell DiseaseLate Stage Preclinical Projects$4,849,363
Dr Jennifer M PuckUniversity of California, San FranciscoEx 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 PorteusStanford UniversityPre-clinical development of gene correction therapy of hematopoietic stem cells for SCID-X1Preclinical Development Awards$874,877
Dr. Hanna MikkolaUniversity of California, Los AngelesA suite of engineered human pluripotent stem cell lines to facilitate the generation of hematopoietic stem cellsTools and Technologies III$1,382,400
Dr. Andrew D. Leavitt MDUniversity of California, San FranciscoSmall molecule tools and scale-up technologies to expand human umbilical cord blood stem and progenitor cells for clinical and research useTools and Technologies III$1,416,600
Dr. Irving L Weissman MDStanford UniversityIdentification 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 TarantalUniversity of California, Davis9th Annual Gene Therapy Symposium for Heart, Lung and Blood DiseasesConference$12,000
Dr. Alice F TarantalUniversity of California, Davis10th Annual Gene Therapy Symposium for Heart, Lung, and Blood DiseasesConference$18,300
Dr. Alice F TarantalUniversity of California, Davis11th Annual Gene Therapy Symposium for Heart, Lung, and Blood DiseasesConference$16,850
Dr. Brian BlackUniversity of California, San FranciscoWeinstein Cardiovascular Development ConferenceConference$35,000
Dr. Donald B. KohnChildren’s Hospital of Los AngelesSTEM CELL GENE THERAPY FOR SICKLE CELL DISEASEDisease Team Planning$12,131
Dr. Dianne McKayUniversity of California, San DiegoRole of intracytoplasmic pattern recognition receptors in HSC engraftmentBasic Biology V$615,639
Dr. Lili YangUniversity of California, Los AngelesDifferentiation of Human Hematopoietic Stem Cells into iNKT CellsBasic Biology V$614,400
Dr. Donald B. KohnUniversity of California, Los AngelesClinical Trial of Stem Cell Gene Therapy for Sickle Cell DiseaseDisease Team Therapy Development III$13,145,465
Dr. Fyodor D UrnovSangamo BioSciences, Inc.A Treatment For Beta-thalassemia via High-Efficiency Targeted Genome Editing of Hematopoietic Stem CellsStrategic Partnership II$2,760,540
Dr. Donald B. KohnUniversity of California, Los AngelesBeta-Globin Gene Correction of Sickle Cell Disease in Hematopoietic Stem CellsEarly Translational IV$1,651,884
Dr. Inder M. VermaSalk Institute for Biological StudiesDevelopment of a cell and gene based therapy for hemophiliaEarly Translational IV$2,298,634
David M. DavidsonBluebird BioA 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 MDUniversity of California, San FranciscoIn Utero Embryonic Stem Cell Transplantation to Treat Congenital AnomaliesNew Faculty Physician Scientist$2,661,742
Ann Capela ZoveinUniversity of California, San FranciscoHuman endothelial reprogramming for hematopoietic stem cell therapy.New Faculty Physician Scientist$2,197,683
Dr. Judith A ShizuruStanford UniversityA monoclonal antibody that depletes blood stem cells and enables chemotherapy free transplantsDisease Team Therapy Development – Research$18,990,683
Dr. Gay Miriam CrooksUniversity of California, Los AngelesForming the Hematopoietic Niche from Human Pluripotent Stem CellsBasic Biology III$1,252,857
Dr. Irving L Weissman MDStanford UniversityAntibody tools to deplete or isolate teratogenic, cardiac, and blood stem cells from hESCsTools and Technologies II$1,463,814
Dr. John P ChuteUniversity of California, Los AngelesNiche-Focused Research: Discovery & Development of Hematopoietic Regenerative FactorsResearch Leadership$4,645,297
Professor Hiromitsu NakauchiStanford UniversityGeneration of functional cells and organs from iPSCsResearch Leadership$5,426,135
Dr. Hanna MikkolaUniversity of California, Los AngelesMechanisms of Hematopoietic stem cell Specification and Self-RenewalNew Faculty I$2,286,900
Dr. Inder M. VermaSalk Institute for Biological StudiesCuring Hematological DiseasesEarly Translational I$5,979,252
Dr. Nicholas R.J. GascoigneScripps Research InstituteRole of Innate Immunity in hematopoeitic stem cell-mediated allograft toleranceTransplantation Immunology$1,705,554
Dr. David H RauletUniversity of California, BerkeleyInactivating NK cell reactivity to facilitate transplantation of stem cell derived tissueTransplantation Immunology$952,896
Dr. Tippi C. Mackenzie MDUniversity of California, San FranciscoMaternal and Fetal Immune Responses to In Utero Hematopoietic Stem Cell TransplantationTransplantation Immunology$1,230,869
Dr. Judith A ShizuruStanford UniversityPurified allogeneic hematopoietic stem cells as a platform for tolerance inductionTransplantation Immunology$1,233,275
Dr. Fred H. GageSalk Institute for Biological StudiesDevelopment of Induced Pluripotent Stem Cells for Modeling Human DiseaseNew Cell Lines$1,737,720
Dr. Irving L Weissman MDStanford UniversityProspective isolation of hESC-derived hematopoietic and cardiomyocyte stem cellsComprehensive Grant$2,471,386
Dr. Hanna MikkolaUniversity of California, Los AngelesImproving microenvironments to promote hematopoietic stem cell development from human embryonic stem cellsSEED Grant$550,241
Dr. Cornelis MurreUniversity of California, San DiegoGeneration of long-term cultures of human hematopoietic multipotent progenitors from embryonic stem cellsSEED Grant$473,952
Dr. Steven Edward ArtandiStanford UniversitySelf-renewal and senescence in iPS cells derived from patients with a stem cell diseaseBasic Biology II$931,285
Dr. Donald B. KohnUniversity of California, Los AngelesStem Cell Gene Therapy for Sickle Cell DiseaseDisease Team Research I$8,833,695
Dr. Luisa Iruela-ArispeUniversity of California, Los AngelesMolecular Characterization and Functional Exploration of Hemogenic EndotheliumBasic Biology I$1,371,477
Total:
$294,056,599.60

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Resources

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