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UC Davis researchers awarded new stem cell grants
Jan Nolta, Ph.D. Vicki Wheelock, M.D.
SACRAMENTO -- The California Institute for Regenerative Medicine (CIRM), the state stem cell agency, has approved two multimillion dollar, multiyear grants for UC Davis Health System researchers to develop a novel stem cell therapy for neurodegenerative disorders such as Huntington's disease and to support the development of treatments for young patients suffering from sickle cell anemia, thalassemia and other inherited blood and metabolic disorders.
The two grants, among 15 early translational funding awards approved by the CIRM governing board earlier this week, focus on moving promising basic scientific research into clinical cures for patients. Each of the UC Davis investigations is specifically designed to overcome bottlenecks in the development of unique stem cell therapies for patients in need.
With a new, $2.7 million grant for Huntington's disease and related disorders, UC Davis scientists hope to create and test a safe and effective therapy that uses mesenchymal stem cells from the bone marrow to reduce levels of the harmful mutant protein that attacks parts of the brain and results in uncontrolled movements, emotional disturbance and loss of intellectual faculties. A separate grant for $4.2 million funds research to safely treat infants in utero to prevent the early and damaging effects of inherited blood cell disorders.
"Today's award from CIRM gives us a terrific boost because it opens the door to developing an innovative and effective therapeutic tool for victims of neurodegenerative disorders like Huntington's disease," said Jan Nolta, principal investigator for the new grant and director of the Stem Cell Program at UC Davis. "Diseases of the brain are incredibly challenging to treat. What we hope to do is create a stem cell-based treatment that can deliver therapeutic molecules directly into damaged cells in the brain."
Nationally, one out of every 10,000 people suffers from Huntington's disease, a disorder of the brain that can appear at any age but most often arises in people between the ages of 35 and 44 years. Multiple generations within a family can inherit the disorder, which touches all races and socioeconomic levels and has no cure. In order to treat Huntington's, affected and dying neurons in the brain would need to be salvaged or replaced. Levels of the toxic mutant protein that causes neural damage and leads to the physical and cognitive problems commonly associated with the disease would also need to be diminished.
Nolta and colleague Vicki Wheelock, an associate professor of neurology and medical director of the UC Davis Movement Disorders Clinic, plan to use a molecular interference strategy called small interfering ribonucleic acid (siRNA) to prevent the neurodegenerative mutant protein from being produced in cells. RNA interference has been very effective in animal models of Huntington's, but remains very difficult to deliver into the brain.
Over the past 20 years, Nolta has shown that mesenchymal stem cells are highly effective delivery tools to distribute proteins and other products throughout many organs. Her group is now engineering these stem cells to produce siRNA designed to target the mutant protein in damaged areas of the brain. The researchers hope that mesenchymal stem cells engineered to deliver the siRNA can be an effective means of infusing therapeutic molecules into each damaged neuron they contact. By exploiting the mesenchymal stem cell's inherent search-and-rescue function, the team hopes to develop a long-lasting therapy that specifically targets the affected regions of the brain, avoiding systemic infusion or repetitive siRNA administration into the central nervous system.
The latest CIRM awards hold great promise for patients and their families.
"This is the best news," said Judy Roberson, president, of the Huntington's Disease Society of America Northern California Chapter. "Families like mine have been waiting for an intervention for Huntington's since the gene was located 16 years ago. My husband and his brother and thousands of others died waiting for something, anything. Now, thanks to CIRM support and the research at UC Davis, there's real hope for the first time."
UC Davis Health System's other CIRM grant offers new ways of overcoming roadblocks to treating inherited diseases of the blood which, while they can be identified before birth, are difficult to effectively treat. Recent studies suggest that very early treatment, before irreversible damage from disease has occurred, provides the best opportunities for both survival and quality of life.
Led by Alice F. Tarantal, professor of pediatrics and associate director of the UC Davis Stem Cell Program, researchers will explore an in utero model to assess the capabilities of transplanted stem cells. They will be looking at whether the stem cells take hold and provide the new cells necessary for therapeutic success. Tarantal and other investigators on her team also will be monitoring the activity and locations of transplanted stem cells as they travel through the body.
The investigation addresses several challenges to translating laboratory research into clinical treatments for young patients, including crucial safety and efficacy issues surrounding the use of umbilical cord blood and cells obtained from human embryonic stem cells. Using a preclinical model in their research will show scientists what happens to stem cells once they are injected and where they ultimately reside. It will provide the scientific insights and understanding necessary for the eventual human transplantation of these cells.
"Our team is poised to address crucial bottlenecks that have delayed these therapies from reaching our youngest patients," said Tarantal. "We greatly appreciate the support provided by CIRM to help us work toward these goals. Infants with congenital blood diseases can be diagnosed before they are born. We hope it may be possible to treat these young patients early and thus avoid the many problems such diseases can cause."
The team of researchers working together on the Tarantal project includes biomedical engineering faculty at UC Davis, and pediatric and other colleagues at UC San Francisco, UCLA and Indiana University School of Medicine.
Tarantal is the previous recipient of a CIRM grant for research into how human embryonic stem cells can be turned into the type of cells needed to regenerate diseased kidneys, a problem that affects thousands of infants born each year in the United States. The state stem cell agency is also funding her study of new, non-invasive imaging technologies that can enhance the ability of scientists to track the movement of stem cells once they have been injected into a target area.
About UC Davis stem cell research
UC Davis is playing a leading role in stem cell research, with more than 125 faculty scientists and physicians working on a variety of stem cell investigations at campus locations in Davis and Sacramento. The university's new Institute for Regenerative Cures, a facility supported by the California Institute for Regenerative Medicine, is currently under construction. This 90,000 square-foot research facility is located in Sacramento and will provide researchers with state-of-the-art laboratories, cell manufacturing and testing rooms, and enable clinical trials to test stem cells therapies. This project, along with the Translational Human Embryonic Stem Cell Shared Research Facility in Davis, complements the university's NIH-supported Clinical and Translational Science Center and help turn stem cells into cures. For more information, visit www.ucdmc.ucdavis.edu/stemcellresearch.