Q&A With Gary Steinberg, MD, PhD Chair, Department of Neurosurgery
Q&A With Gary Steinberg, MD, PhD & Chair, Department of Neurosurgery
Gary Steinberg, MD, PhD
Stanford’s Gary Steinberg, MD, PhD, has an international reputation as a neurosurgeon. For more than 16 years, he has chaired the Department of Neurosurgery at Stanford and pioneered life-saving surgical procedures for several complex brain conditions. People with Moyamoya, a rare cerebrovascular disease, travel from around the world to be his patients.
His groundbreaking research, however, is pushing for biological treatments. Twice this year, Steinberg has gone into an operating room to insert cells that might restore function to those who have suffered strokes or spinal cord injuries. Stanford was the first institution in the U.S. to test the safety of a new form of adult-derived cell called SB623. The trial is the first to test a cellular therapy for stroke delivered directly to the brain. The other trial is the first to clinically test the use of embryonic stem cells-this time in patients with recent spinal cord injury caused by trauma. Stanford is one of seven institutions in the U.S. to participate in that trial. Steinberg is the principal investigator at Stanford for both trials.
You’ve recently completed two procedures in landmark clinical trials that hope to revolutionize medical therapies in two significant medical illnesses: spinal cord paralysis and stroke. Please describe the procedures.
We treated the spinal cord injured paraplegic patient with embryonic stem cells developed by researchers at the Geron Corp. in Menlo Park and UC-Irvine. The original cells had been coaxed into becoming precursors to oligodendrocytes, which produce myelin. Myelin surrounds neural axons and without it, nerves don’t work. If the spinal cord is damaged by a blunt injury, the myelin falls apart, and nerves won’t work then either. We inserted about two million of these specially-prepared cells into the damaged area of the spinal cord. We placed the cells in the damaged tissue and hope they will mature into myelin-producing cells that will reinsulate the affected nerves and make them functional again. This approach has been shown to work in animal models.
In the second procedure we used cells derived from adult bone marrow. They’re called SB623 cells and were developed by SanBio Inc. We inserted these cells into the area of the patient’s brain damaged by an ischemic stroke. They have been engineered by SanBio to express a gene that regulates development. The idea is to revive function by secreting growth factors and other proteins that stimulate endogenous mechanisms of brain recovery.
One of the clinical trials used embryonic stem cells and the other used cell therapy. Explain the difference?
Embryonic stem cells are produced from fertilized eggs that have reached the blastocyst stage – that’s five days after fertilization. They can become any type of cell in the body. They are also easy to grow in a culture. Large numbers of cells – in the millions – are needed for cell therapy, so that characteristic is important.
We also can use stem cells from adults, which used to be thought to be less vigorous and versatile, but that’s all changed now. Recent research has shown there are ways to manipulate those cells down nearly any path you want. Dr.Renee Reijo Pera, director of our Center for Reproductive and Stem Cell Biology and our Center for Human Embryonic Stem Cell Research and Education, and Dr. Theo Palmer, another one of our prominent stem cell investigators, are now turning human skin cells into neuronal cells, which may lead to a method for repairing the damage of Parkinson’s disease with cells from one’s own body. All the technologies to develop new cells are developing very rapidly.
What previous medical breakthroughs lead you to believe that there might be a non-surgical, non-pharmaceutical method of treatment?
The track record with bone marrow transplant has revolutionized the treatment of lymphoid cancer and other similar forms of cancer. Instead of chemotherapy or radiation, which work to physically destroy cells, bone marrow transplants – and stem cell transplants–manipulate the natural processes in the body to act against injury or disease.
How did you begin your work?
I became interested in the potential applications of stem cell therapy for treating neurologic disorders about a decade ago. Using animal models of stroke, we first looked at where to put stem cells. If we put them too close to an area damaged by stroke, they would die because there was no blood flow to that area. The next time, we tried putting the cells a few millimeters outside the stroke area and they survived and we ultimately observed some recovered motor sensory behavior. We were also developing methods to monitor the cells in real time by adding iron to them so they could be tracked by magnetic resonance scans. We discovered that these cells pick up cues from the environment in a bi-directional kind of communication. We also figured out that the normal brain of an adult does make new neural cells after injury, although not very many and not enough to regenerate tissue in the way that the liver, skin and bone does. Once we knew that, we focused on just how that was happening. We found that the cells boost our native growth mechanisms – and they have a profound effect on stimulating new blood vessels in an injured area. They also act to blunt inflammation. Driving all this was a protein produced by the cells called vascular endothelial growth factor–VEGF.
How do you think the unexpected end of the Geron trial will affect the future of this type of therapy?
While we were all disappointed in Geron’s decision to halt enrollment in this study and to abandon their stem cell program, we should remember that five of the anticipated eight total patients were successfully transplanted with no adverse effects noted to date. Since this was designed as a safety study, the outcomes are very encouraging. These patients will be followed for 15 years to assess continued safety as well as any signs of neurologic improvement. I don’t believe the early termination of enrollment in this study will significantly set back the stem cell therapy field.
What has been your personal motivation to pursue and study embryonic stem cell treatment?
I was inspired by what I see every day: Patients devastated by neurological disorders and psychiatric disease with no hope or little hope for recovery of function. And it’s been like that for hundreds of years for many neurological diseases or injuries, including stroke, degenerative disorders like Parkinson’s, brain tumors, Alzheimer’s. These patients are disabled and we have no treatment once the injury has occurred to restore or regenerate function. Stem cell therapy offers great hope to change that status for a large number of patients.
Do you expect to see improvements in patients recently treated with cell therapy?
These are studies to test the safety of these treatments, to test for possible adverse effects. It would be wonderful if we saw some small benefits. The first patient in the SanBio trial received the treatment twoyears after the stroke. Some believe that to see benefits, we’d have to transplant sooner, within one week to one month.
What are the questions that must be answered before this type of cell therapy is widely available?
We need to know which patients will respond, the optimal numbers of cells to transplant, the route of delivery and the timing. We want to be cautious. I think it will be a five-to 10-year time table before we’ll reap the benefits of this novel therapeutic strategy and possibly see significant recovery.
By Sara Wykes
Stanford University Medical Center
About Stanford Hospital & Clinics
Stanford Hospital & Clinics is known worldwide for advanced treatment of complex disorders in areas such as cardiovascular care, cancer treatment, neurosciences, surgery, and organ transplants. It is currently ranked No. 17 on the U.S. News & World Report’s “America’s Best Hospitals” list and No. 1 in the San Jose Metropolitan area. Stanford Hospital & Clinics is internationally recognized for translating medical breakthroughs into the care of patients. The Stanford University Medical Center is comprised of three world renowned institutions: Stanford Hospital & Clinics, the Stanford University School of Medicine, the oldest medical school in the Western United States, and Lucile Packard Children’s Hospital, an adjacent pediatric and obstetric teaching hospital providing general acute and tertiary care. For more information, visit http://stanfordhospital.org/
* Stanford University Medical Center integrates research, medical education and patient care at its three institutions – Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children’s Hospital.
** The above story is adapted from materials provided by Stanford University School of Medicine