The great hope for stem cell research is the development of treatments for devastating diseases. UCSF basic science and clinical research teams are at the forefront of this effort.

In studies conducted in the culture dish and in animals, scientists are learning how to prompt stem cells to develop into so-called adult, or specialized, cells of tissues such as the heart, pancreas and brain. The ultimate goal of these studies is to transplant  specialized cells, such as heart cells, into patients to regenerate damaged tissues.

David Rowitch, MD, PhD

David Rowitch, MD, PhD

UCSF scientists also are exploring the use of stem cells as vehicles for delivering drugs into diseased tissues.  In addition, they are using specialized cells produced by stem cells, such as liver cells, to test the effectiveness of experimental drugs in the culture dish. In other studies, they are investigating the role of stem cells in generating many forms of cancer, an important first step for targeting the cells for therapies.

UCSF clinical researchers also have begun one of the first early-stage stem cell clinical trials in the United States, and have other potential trials on the horizon. Early-stage trials are intended, foremost, to test the safety of a therapeutic approach, although evidence of treatment is also examined.

Clinical Trial for Rare Brain Disease

UCSF is conducting a phase I clinical trial to test the safety and preliminary effectiveness of using neural stem cells to treat children with a rare, fatal form of a disorder named Pelizaeus-Merzbacher disease, known as PMD. Currently, there are no effective treatments for fatal types of the disease, which affects males who inherit a single defective gene. This trial is led by David Rowitch, MD, PhD, a pediatric specialist and chief of Neonatology at UCSF Benioff Children’s Hospital.

“Severe PMD is a devastating illness that globally affects brain function, yet we know that it is caused solely by defects in a single type of brain cell, the oligodendrocyte,” says Rowitch. “This FDA-authorized phase I trial will help us to judge whether cellular replacement of defective cells in the brain is safe for patients with PMD. We hope to open a window on a treatment strategy for PMD and other oligodendrocyte-based diseases for which we don’t have treatments. It is terribly important to be able to offer new prospects for these children.”

The clinical trial is the first neural stem cell trial in the United States designed to treat a disease resulting from a lack of myelin, a substance that insulates the communication fibers, or axons, that extend from the bodies of nerve cells. Without myelin, short circuits occur when nerve cells try to send electrochemical signals to one another through the axons.

The cells that make myelin are called oligodendrocytes. Damage to these cells is also the hallmark of multiple sclerosis and is implicated in certain forms of cerebral palsy. The ultimate goal of the treatment strategy is for the neural stem cells to integrate into the neural circuitry of the damaged brain region and develop into functioning oligodendrocytes. Successful studies in mice demonstrated the potential of the approach.

The clinical trial, which Rowitch is conducting in collaboration with neurosurgeons and neurologists, is the second neural stem cell trial authorized to be conducted in the United States.  The first was conduced at Oregon Health & Science University.  There, clinicians have already completed a phase 1 study, and recently began a phase 1-b study, using the same cells currently being tested in PMD patients to treat another rare, fatal neurodegenerative disease known as Batten disease.  In the case of Batten disease, these cells are being evaluated for their ability to replace a missing enzyme - rather than missing oligodendrocytes. 

Both studies are sponsored by StemCells, Inc., whose proprietary, purified human neural stem cells are used in the trials. The long-term goal of both studies is to see whether the cells preserve or restore neurological function in patients afflicted by these devastating diseases.

Potential Trials on Diabetes, Brain Tumors

Two UCSF teams are working to lay the groundwork for diabetes and brain tumor clinical trials.

Each team’s goal is to file a new drug application to the Food and Drug Administration within four years. The trials are funded by grants from the California Institute for Regenerative Medicine, the state agency created to award $3 billion in grants for stem cell research in California over the course of 10 years. The decision to fund the research was the result of a state proposition passed in 2004.

  • The diabetes grant is co-led by Peter Stock, MD, PhD, UCSF professor of surgery, in collaboration with ViaCyte Inc. The team’s strategy is to encapsulate islet progenitor cells generated from human embryonic stem cells in a durable, retrievable device and to implant them into patients. The cells, which differentiate into glucose-responsive islet beta cells after transplantation, have proven to be a successful strategy in treating rodents with chemically induced diabetes.
  • The brain tumor grant is led by Mitchel Berger, MD, chair of the UCSF Department of Neurological Surgery, in collaboration with the Ludwig Institute for Cancer Research and the Burnham Institute for Medical Research. The team is working to refine a strategy in which adult and fetal neural stem cells are genetically engineered to contain a tumor-killing gene that would home in on glioblastoma multiforme, the most common and aggressive form of brain tumor. The studies in rodents engineered to develop human brain tumors were successful. The team is investigating the same strategy using mesenchymal cells, which give rise to skeletal tissues.