While stem cell and gene therapy research has advanced dramatically in recent years, there are still many unknowns and many questions remaining about how best to use these approaches in developing therapies. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) today approved investing almost $25 million in 19 projects in early stage or Discovery research.
The awards are from CIRM’s DISC2 Quest program, which supports the discovery of promising new stem cell-based and gene therapy technologies that could be translated to enable broad use and ultimately, improve patient care.
“Every therapy that helps save lives or change lives begins with a researcher asking a simple question, “What if?”, says Dr. Maria T. Millan, the President and CEO of CIRM. “Our Quest awards reflect the need to keep supporting early stage research, to gain a deeper understanding of stem cells work and how we can best tap into that potential to advance the field.”
Dr. Judy Shizuru at Stanford University was awarded $1.34 million to develop a safer, less-toxic form of bone marrow or hematopoietic stem cell transplant (HCT). HCT is the only proven cure for many forms of blood disorders that affect people of all ages, sexes, and races worldwide. However, current methods involve the use of chemotherapy or radiation to destroy the patient’s own unhealthy blood stem cells and make room for the new, healthy ones. This approach is toxic and complex and can only be performed by specialized teams in major medical centers, making access particularly difficult for poor and underserved communities.
Dr. Shizuru proposes developing an antibody that can direct the patient’s own immune cells to kill diseased blood stem cells. This would make stem cell transplant safer and more effective for the treatment of many life-threatening blood disorders, and more accessible for people in rural or remote parts of the country.
Dr. Lili Yang at UCLA was awarded $1.4 million to develop an off-the-shelf cell therapy for ovarian cancer, which causes more deaths than any other cancer of the female reproductive system.
Dr. Yang is using immune system cells, called invariant natural killer T cells (iNKT) to attack cancer cells. However, these iNKT cells are only found in small numbers in the blood so current approaches involve taking those cells from the patient and, in the lab, modifying them to increase their numbers and strength before transplanting them back into the patient. This is both time consuming and expensive, and the patient’s own iNKT cells may have been damaged by the cancer, reducing the likelihood of success.
In this new study Dr. Yang will use healthy donor cord blood cells and, through genetic engineering, turn them into the specific form of iNKT cell therapy targeting ovarian cancer. This DISC2 award will support the development of these cells and do the necessary testing and studies to advance it to the translational stage.
Timothy Hoey and Tenaya Therapeutics Inc. have been awarded $1.2 million to test a gene therapy approach to replace heart cells damaged by a heart attack.
Heart disease is the leading cause of death in the U.S. with the highest incidence among African Americans. It’s caused by damage or death of functional heart muscle cells, usually due to heart attack. Because these heart muscle cells are unable to regenerate the damage is permanent. Dr. Hoey’s team is developing a gene therapy that can be injected into patients and turn their cardiac fibroblasts, cells that can contribute to scar tissue, into functioning heart muscle cells, replacing those damaged by the heart attack.
The full list of DISC2 Quest awards is:
|APPLICATION NUMBER||TITLE OF PROGRAM||PRINCIPAL INVESTIGATOR||AMOUNT|
|DISC2-13400||Targeted Immunotherapy-Based Blood Stem Cell Transplantation||Judy Shizuru, Stanford Universtiy||$1,341,910|
|DISC2-13505||Combating Ovarian Cancer Using Stem Cell-Engineered Off-The-Shelf CAR-iNKT Cells||Lili Yang, UCLA||$1,404,000|
|DISC2-13515|| A treatment for Rett syndrome using glial-restricted|
neural progenitor cells
|Alysson Muotri, UC San Diego||$1,402,240|
|DISC2-13454||Targeting pancreatic cancer stem cells with DDR1 antibodies.||Michael Karin, UC San Diego||$1,425,600|
|DISC2-13483||Enabling non-genetic activity-driven maturation of iPSC-derived neurons||Alex Savtchenko, Nanotools Bioscience||$675,000|
|DISC2-13405|| Hematopoietic Stem Cell Gene Therapy for Alpha|
|Don Kohn, UCLA||$1,323,007|
|DISC2-13507|| CAR T cells targeting abnormal N-glycans for the|
treatment of refractory/metastatic solid cancers
|Michael Demetriou, UC Irvine||$1,414,800|
|DISC2-13463|| Drug Development of Inhibitors of Inflammation Using|
Human iPSC-Derived Microglia (hiMG)
|Stuart Lipton, Scripps Research Inst.||$1,658,123|
|DISC2-13390||Cardiac Reprogramming Gene Therapy for Post-Myocardial Infarction Heart Failure||Timothy Hoey, Tenaya Therapeutics||$1,215,000|
|DISC2-13417||AAV-dCas9 Epigenetic Editing for CDKL5 Deficiency Disorder||Kyle Fink, UC Davis||$1,429,378|
|DISC2-13415|| Defining the Optimal Gene Therapy Approach of|
Human Hematopoietic Stem Cells for the Treatment of
Dedicator of Cytokinesis 8 (DOCK8) Deficiency
|Caroline Kuo, UCLA||$1,386,232|
|DISC2-13498|| Bioengineering human stem cell-derived beta cell|
organoids to monitor cell health in real time and improve therapeutic outcomes in patients
|Katy Digovich, Minutia, Inc.||$1,198,550|
|DISC2-13469|| Novel antisense therapy to treat genetic forms of|
|Joseph Gleeson, UC San Diego||$1,180,654|
|DISC2-13428||Therapeutics to overcome the differentiation roadblock in Myelodysplastic Syndrome (MDS)||Michael Bollong, Scripps Research Inst.||$1,244,160|
|DISC2-13456||Novel methods to eliminate cancer stem cells||Dinesh Rao, UCLA||$1,384,347|
|DISC2-13441|| A new precision medicine based iPSC-derived model to study personalized intestinal fibrosis treatments in|
pediatric patients with Crohn’s diseas
|Robert Barrett Cedars-Sinai||$776,340|
|DISC2-13512|| Modified RNA-Based Gene Therapy for Cardiac|
Regeneration Through Cardiomyocyte Proliferation
|Deepak Srivastava, Gladstone Institutes||$1,565,784|
|DISC2-13510|| An hematopoietic stem-cell-based approach to treat HIV employing CAR-T cells and anti-HIV broadly|
|Brian Lawson, The Scintillon Institute||$1,143,600|
|DISC2-13475||Developing gene therapy for dominant optic atrophy using human pluripotent stem cell-derived retinal organoid disease model||Xian-Jie Yang, UCLA||$1,345,691|