February 11, 2011
David Rowitch, a UCSF neonatologist and Howard Hughes Medical Institute investigator, examines a newborn baby at UCSF Benioff Childrens Hospital. He is involved in a Phase I safety study sponsored by StemCells, Inc. for a potential new therapy for connatal Pelizaeus-Merzbacher Disease (PMD), which is a rare inherited condition involving the central nervous system.
Stem cell science remains a fast-moving frontier – that much was made clear by leading scientists discussing their latest discoveries on Feb. 9 during a scientific symposium honoring the opening of the Ray and Dagmar Dolby Regeneration Medicine Building on the UCSF Parnassus campus.
The full-house audience in Cole Hall auditorium heard talks from several academic scientists, among them keynote speaker Shinya Yamanaka, MD, PhD, a UCSF professor and Gladstone Institutes investigator who revolutionized stem cell research by learning to induce adult cells to become pluripotent stem cells.
But the translation of that science into treatment is a bit of a frontier, too. The US Food and Drug Administration (FDA) is more accustomed to regulating drugs that are small molecules or proteins. The evaluation of drugs that are cells is still evolving. Cell treatments developed using stem cell techniques have only recently entered clinical trials and to date none have been approved for standard medical practice.
The Feb. 9 symposium concluded with brief presentations about the development of stem cell therapies and groundbreaking clinical trials by leading scientists from California companies. They served as the panel for a roundtable discussion of questions raised by audience members.
Alexandra Capela, PhD, a research scientist from Palo Alto-based StemCells Inc. discussed a decade-long program through which the company has developed neural stem cells for the treatment of several medical conditions. The human stem cell line the company is commercializing can generate cells of the nervous system, including neurons, astrocytes and oligodendrocytes. The company earlier completed a Phase I trial in which the cells were well tolerated in six patients with advanced stages of a rare and normally fatal disease called infantile neuronal ceroid lipofuscinosis.
Working with UCSF pediatrician and scientist David Rowitch, MD, PhD, StemCells Inc. now is conducting a Phase I trial in another rare and fatal brain disorder called Pelizaeus-Merzbacher Disease (PMD), in which the protective myelin sheath fails to develop around nerves. Nerves cannot signal normally in infants afflicted with the disease. Intellectual and motor development is limited, and most affected children die by age 10. Rowitch hopes the clinical trial for PMD, which is now open for enrollment, will improve the understanding of more common disorders like multiple sclerosis and cerebral palsy.
In addition, the StemCells Inc. is engaged in pre-clinical studies and aims to develop protocols to treat more common, less fatal diseases, including other disorders involving loss of myelin, and age-related macular degeneration. The company has been authorized to begin treating spinal cord injury in a Swiss clinical trial.
Kevin D'Amour, PhD, principal scientist at San Diego-based ViaCyte Inc. described pre-clinical studies of a stem cell therapy for diabetes. The treatment aims to replace insulin-secreting beta cells of the pancreas that are destroyed by the immune system. ViaCyte Inc. has used a National Institutes of Health-approved embryonic stem cell line to develop more specialized, but not yet fully differentiated cells that act as beta-cell-generating stem cells when implanted in the patient.
The company developed a removable capsule in which to implant the cells beneath the skin. The capsule protects the cells from immune attack, but allows the beta cells to function. The cells mature, sense glucose and secreting insulin. ViaCyte Inc. earlier received a $20 million grant from the California Institute for Regenerative Medicine, and the company has contracted with UCSF Diabetes Center researchers Jeffrey Bluestone, PhD, executive vice chancellor and provost at UCSF, Matthias Hebrok, PhD, director of the Diabetes Center at UCSF, and Michael German, MD, to further preclinical development of the therapy.
David Piper, PhD, research and development manager for Carlsbad-based Life Technologies Corporation, described several of the company's advanced laboratory technologies that can be useful in the development of stem cell therapies and other laboratory research. Among them is the new DNA-sequencing device called the Personal Genome Machine, which is the size of a desktop printer.
"It's lower cost than most everything on the market," Piper said. "The speed is remarkable."
Joseph Gold, PhD, senior director of stem cell biology and research operations for Geron Corporation and a former UCSF postdoctoral fellow, described the ongoing development of stem cell treatments. The company became the first to launch US stem cell therapy trials for spinal cord injury last year, using oligodendrocyte progenitor cells developed from human embryonic stem cells.
The company also is targeting other tissues and medical conditions. Among the stem cell products under development are cardiomyocytes to replace heart muscle in heart failure patients, endocrine cell precursors for diabetes and chondrocytes cells for cartilage repair.
Gold noted that the regulatory bar is being raised for manufacturing processes being used for stem cell therapies, including requirements related to growth media for cells, which previously relied on animal-derived substances.
"The goal is to remove anything that is not going to be an easy path to the clinic. … Don't even start with materials that are going to be problematic," he said.
Gold and others said that discussions with staff at the FDA have been fruitful. "There have been very good discussions going back and forth. They are not necessarily naysayers for the sake of being naysayers. They're really trying to do their job and to make sure things are safe. The discussions we have had have actually been very good and beneficial. I don't want you to think it's a regulatory environment that will shut you down."
Regarding StemCells Inc.'s own interactions with the federal agency, Capela added, "It's been a learning experience for both parties."
Photo by Peter DaSilva