It’s appropriate that at the start of Women’s History Month, UC Davis’ Dr. Diana Farmer is making a little history of her own. She launched the world’s first clinical trial using stem cells to treat spina bifida before the child is born.
Spina bifida is a birth defect caused when a baby’s spinal cord fails to develop properly in the womb. In myelomeningocele, the most severe form of spina bifida, a portion of the spinal cord or nerves is exposed in a sac through an opening in the spine. Most people with myelomeningocele have changes in their brain structure, leg weakness, and bladder and bowel dysfunction.
While surgery can help, Dr. Farmer says it is far from perfect: “Currently, the standard of care for our patients is fetal surgery, which, while promising, still leaves more than half of children with spina bifida unable to walk independently. There is an extraordinary need for a treatment that prevents or lessens the severity of this devastating condition. Our team has spent more than a decade working up to this point of being able to test such a promising therapy.”
The team at UC Davis – in a CIRM-funded study – will use a stem cell “patch” that is placed over the exposed spinal cord, then surgically close the opening, hopefully allowing the stem cells to regenerate and protect the spinal cord.
In a news release Dr. Aijun Wang, a stem cell bioengineer, says the team has been preparing for this trial for years, helping show in animals that it is safe and effective. He is hopeful it will prove equally safe and effective in people: “Our cellular therapy approach, in combination with surgery, should encourage tissue regeneration and help patients avoid devastating impairments throughout their lives.”
Dr. Farmer says the condition, while rare, disproportionately affects Latinx babies and if the procedure works could have an enormous impact on their lives and the lives of their families: “A successful treatment for MMC would relieve the tremendous emotional and economic cost burden on families. We know it initially costs approximately $532,000 per child with spina bifida. But the costs are likely several million dollars more due to ongoing treatments, not to mention all the pain and suffering, specialized childcare, and lost time for unpaid caregivers such as parents.”
Here is video of two English bulldogs who had their spinal injuries repaired at UC Davis using stem cells. This was part of the research that led to the clinical trial led by Dr. Farmer and Dr. Wang.
This past Thursday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved four new clinical trials in addition to ten new discovery research awards.
These new awards bring the total number of CIRM-funded clinical trials to 68. Additionally, these new additions have allowed the state agency to exceed the goal of commencing 50 new trials outlined in its five year strategic plan.
$8,970,732 was awarded to Dr. Steven Deeks at the University of California San Francisco (UCSF) to conduct a clinical trial that modifies a patient’s own immune cells in order to treat and potentially cure HIV.
Current treatment of HIV involves the use of long-term antiretroviral therapy (ART). However, many people are not able to access and adhere to long-term ART.
Dr. Deeks and his team will take a patient’s blood and extract T cells, a type of immune cell. The T cells are then genetically modified to express two different chimeric antigen receptors (CAR), which enable the newly created duoCAR-T cells to recognize and destroy HIV infected cells. The modified T cells are then reintroduced back into the patient.
The goal of this one time therapy is to act as a long-term control of HIV with patients no longer needing to take ART, in effect a form of HIV cure. This approach would also address the needs of those who are not able to respond to current approaches, which is estimated to be 50% of those affected by HIV globally.
$3,728,485 was awarded to Dr. Gayatri Rao from Rocket Pharmaceuticals to conduct a clinical trial using a gene therapy for infantile malignant osteopetrosis (IMO), a rare and life-threatening disorder that develops in infancy. IMO is caused by defective bone cell function, which results in blindness, deafness, bone marrow failure, and death very early in life.
The trial will use a gene therapy that targets IMO caused by mutations in the TCIRG1 gene. The team will take a young child’s own blood stem cells and inserting a functional version of the TCIRG1 gene. The newly corrected blood stem cells are then introduced back into the child, with the hope of halting or preventing the progression of IMO in young children before much damage can occur.
Rocket Pharmaceuticals has used the same gene therapy approach for modifying blood stem cells in a separate CIRM funded trial for a rare pediatric disease, which has shown promising results.
$8,996,474 was awarded to Dr. Diana Farmer at UC Davis to conduct a clinical trial of in utero repair of myelomeningocele (MMC), the most severe form of spina bifida. MMC is a birth defect that occurs due to incomplete closure of the developing spinal cord, resulting in neurological damage to the exposed cord. This damage leads to lifelong lower body paralysis, and bladder and bowel dysfunction.
Dr. Farmer and her team will use placenta tissue to generate mesenchymal stem cells (MSCs). The newly generated MSCs will be seeded onto an FDA approved dural graft and the product will be applied to the spinal cord while the infant is still developing in the womb. The goal of this therapy is to help promote proper spinal cord formation and improve motor function, bladder function, and bowel function.
$8,333,581 was awarded to Dr. David Williams at Boston Children’s Hospital to conduct a gene therapy clinical trial for sickle cell disease (SCD). This is the second project that is part of an agreement between CIRM and the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, to co-fund cell and gene therapy programs under the NHLBI’s “Cure Sickle Cell” Initiative. The goal of this agreement is to markedly accelerate clinical development of cell and gene therapies to cure SCD.
SCD is an inherited disease caused by a single gene mutation resulting in abnormal hemoglobin, which causes red blood cells to ‘sickle’ in shape. Sickling of red blood cells clogs blood vessels and leads to progressive organ damage, pain crises, reduced quality of life, and early death.
The team will take a patient’s own blood stem cells and insert a novel engineered gene to silence abnormal hemoglobin and induce normal fetal hemoglobin expression. The modified blood stem cells will then be reintroduced back into the patient. The goal of this therapy is to aid in the production of normal shaped red blood cells, thereby reducing the severity of the disease.
“Today is a momentus occasion as CIRM reaches 51 new clinical trials, surpassing one of the goals outlined in its five year strategic plan,” says Maria T. Millan, M.D., President and CEO of CIRM. “These four new trials, which implement innovative approaches in the field of regenerative medicine, reflect CIRM’s ever expanding and diverse clinical portfolio.”
The Board also approved ten awards that are part of CIRM’s Quest Awards Prgoram (DISC2), which promote promising new technologies that could be translated to enable broad use and improve patient care.
The awards are summarized in the table below:
Human-induced pluripotent stem cell-derived glial enriched progenitors to treat white matter stroke and vascular dementia.
Development of COVID-19 Antiviral Therapy Using Human iPSC-Derived Lung Organoids
UC San Diego
Hematopoietic Stem Cell Gene Therapy for X-linked Agammaglobulinemia
Development of a SYF2 antisense oligonucleotide (ASO) treatment for ALS
University of Southern California
Dual angiogenic and immunomodulating nanotechnology for subcutaneous stem cell derived islet transplantation for the treatment of diabetes
Human iPSC-derived chimeric antigen receptor-expressing macrophages for cancer treatment
UC San Diego
Optimization of a human interneuron cell therapy for traumatic brain injury
Combating COVID-19 using human PSC-derived NK cells
City of Hope
The First Orally Delivered Cell Therapy for the Treatment of Inflammatory Bowel Disease
Transplantation of Pluripotent Stem Cell Derived Microglia for the Treatment of Adult-onset Leukoencephalopathy (HDLS/ALSP)