The researchers are Gary Steinberg, MD, PhD, professor of neurosurgery and neurosciences; Crystal Mackall, MD, professor of pediatrics and of medicine and director of the Stanford Center for Cancer Cell Therapy; and Joseph Wu, MD, PhD, professor of cardiovascular medicine and radiology and the director of the Stanford Cardiovascular Institute.

“The three grants approved today bring forward regenerative medicine clinical trials for brain tumors, stroke, and heart failure, debilitating and fatal conditions where there are currently no definitive therapies or cures,” Maria Millan, MD, president and CEO of CIRM, said in a press release distributed by the institute.

A look at stroke treatment

Steinberg, who holds the Bernard and Ronni Lacroute-William Randolph Hearst Professorship of Neurosurgery and the Neurosciences, received nearly $12 million to investigate whether neural stem cells can help stroke survivors regain mobility. “There are currently more than 7 million stroke survivors in the United States alone who are disabled and with no approved treatment available to improve their condition,” Steinberg said. “This trial will transplant embryonic-derived neural stem cells developed in my lab into the brains of about 20 such patients between six months and five years after their stroke.” The trial is the only ongoing stroke study in North America in which stem cells will be injected directly into the brain.

“We aim to demonstrate safety and feasibility,” Steinberg said, “but our ultimate goal is to restore motor and neurologic function in stroke patients.”

Investigating new uses of CAR-T cell therapy

Mackall, the Ernest and Amelia Gallo Family Professor, was awarded nearly $12 million to investigate whether CAR-T cell therapy, a type of immunotherapy that has been approved to treat several types of blood cancers, can be modified to target a brain and spinal cord cancer called diffuse midline glioma.

“These cancers afflict children and young adults, most of whom die within 18 months of their diagnosis,” Mackall said. Mackall and Michelle Monje, MD, PhD, associate professor of neurology and neurological sciences, have modified the CAR-T cells to recognize a protein called GD2 that is expressed at high levels in glioma cells. “We have seen early signs of activity and acceptable toxicity,” Mackall said. “This award will enable the completion of this trial to determine the optimal route, dose and schedule to determine whether these modified CAR-T cells are effective against this deadly tumor.”

Hoping to improve heart function

Wu, the Simon H. Stertzer, MD, Professor, received nearly $7 million to investigate whether stem-cell-derived heart muscle cells called cardiomyocytes can improve heart function and heart failure symptoms in people with chronic ischemic cardiomyopathy. The heart condition is caused by a restriction in blood supply after a heart attack, which causes the organ to form a scar that eventually causes it to fail. The cardiomyocytes will be administered at the site of the damage. The researchers plan to enroll 18 patients to evaluate three different doses of the cells.

“This phase 1 trial will determine whether transplanting these stem-cell-derived cardiomyocytes is safe and, if so, help us determine the appropriate dose to use in a subsequent phase 2 trial,” Wu said.

More research into stem cells’ use

Four other Stanford researchers also received awards from CIRM to promote the discovery of new stem-cell-based and gene-therapy technologies that could be broadly useful in patient care.

Marius Wernig, MD, professor of pathology, was awarded nearly $1.5 million to continue studies into using next-generation gene editing — induced pluripotent stem cell technology and tissue engineering — to create a skin sheet for patients with dystrophic epidermolysis bullosa, a blistering skin disease.

Phillip Yang, MD, professor of cardiovascular medicine, was awarded nearly $1.5 million to explore whether induced pluripotent stem cells under low-oxygen conditions release substances that can aid in the repair of damaged heart muscle tissue. 

Kathleen Sakamoto, MD, PhD, professor of pediatrics and Shelagh Galligan Professor, was awarded nearly $850,000 to study small-molecule inhibitors of a protein involved in Diamond-Blackfan anemia, a rare inherited bone marrow failure syndrome diagnosed during early childhood. Patients with the condition are treated with steroids, repeated red blood cell transfusions or stem cell transplantation.

Stanley Qi, PhD, assistant professor of bioengineering and of chemical and systems biology, was awarded over $700,000 to develop a novel form of the gene editing tool CRISPR to disturb gene networks and explore new ways to engineer human-induced pluripotent stem cells.