Gene therapy is a new approach to the treatment of many blood cell diseases that may provide an alternative to transplantation from another person. In gene therapy, the bone marrow is collected from the patient’s own body. Next, the stem cells are isolated in the laboratory and a normal copy of the relevant gene (one that produces normal hemoglobin) is either added to the cells or the defective gene of the patient is directly repaired. The gene-corrected stem cells are then transplanted back to the patient after they receive chemotherapy.

In theory, gene therapy should be able to have the same benefits as a bone marrow transplant from another person, but not have risks for graft versus host disease, since it is an autologous (stem cells harvested from self) transplant from the patient.

Research to develop methods for effective gene therapy has been ongoing for more than 20 years. It has been applied successfully to treat more than 50 infants with severe combined immune deficiency (SCID –also known as “bubble baby disease”), with recovery of their immune system after transplant of their own gene-corrected bone marrow. However, gene therapy can have a unique risk in that the methods used to add or fix the gene in the stem cells can trigger overgrowth of the cell, and in some cases caused a leukemia-like disease in treated patients. Newer methods to add or correct genes have been developed and are being studied in current trials for SCID and other diseases. Similar approaches for gene therapy of sickle cell disease are being developed and clinical trials will begin in the near future to determine if they provide a safe and effective way to treat sickle cell disease.

The research for stem cell gene therapy for sickle cell disease is a program of UCLA conducted by Dr. Kohn. His multi-disciplinary disease team includes experts in stem cell gene therapy, clinical bone marrow transplantation, and the care of patients with sickle cell disease.

With your continual contributions and support for research, Hina Patel Foundation remains hopeful that efforts of the UCLA team will find a safe cure for sickle cell disease.

UPDATE:  MAY 2020

Per Dr. Kohn, they have moved forward with the clinical trial of gene therapy for sickle cell disease. In August 2019, a second patient (the first was in 2015) passed the eligibility tests and was enrolled in the trial. Since that time, they have added the anti-sickling gene (Beta-AS3-globin) to the patient’s stem cells. Initially, the patient’s stem cells did not easily move out of the bone marrow into the blood stream (mobilization) with the agent plerixafor (bone marrow stimulant) and required three separate mobilization and collection cycles to obtain sufficient cells. These cells are now ready, however treatment is delayed until the numbers of COVID-19 patients in the hospital decline (now working toward transplant end of June) . Two additional patients are completing work-ups for trial eligibility, which is also on hold due to COVID-19. This clinical trial is funded through a grant from the California Institute for Regenerative Medicine (CIRM) and they anticipate having sufficient funds to complete the trial over the next year.

In addition, they have developed and improved the lentiviral vector through extensive studies led by an MD, PhD student in the lab of Dr. Richard Morgan. In results published this year (Morgan et al Molecular Therapy, 2020), they describe a significantly smaller lentiviral vector that has superior performance, compared to the original vector they used, which is similar to the one developed by bluebird bio. The new smaller vector (called Mini-G) is produced at nearly 10-times higher amounts and gets into stem cells 3-45 times more effectively. If this vector is found to be efficacious in clinical trials, it could greatly lower the overall cost for gene therapy by decreasing vector costs, a major funding component of gene therapy. They have applied to the National Heart, Lung and Blood Institute (NHLBI) Cure Sickle Cell Disease program for a grant to perform the needed pre-clinical studies to move the vector to a clinical trial.

Finally, they continue to explore CRISPR gene editing as an alternative approach to gene therapy for sickle cell disease. In collaboration with Dr. Mark Walters at Oakland Children’s and Dr. Fyodor Urnov at the Innovative Genomics Institute at UC Berkeley, their work is in the final pre-clinical stage (funded by a CIRM CLIN-1 award). They are on target to submit an IND application to begin a clinical trial and will seek additional funding from either CIRM’s remaining Sickle Cell funds or the NHLBI Cure Sickle Cell program.