Two scientists with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have been awarded more than $3.6 million in state grants to develop innovative tools and technologies that will help overcome technical hurdles in advancing basic, translational and clinical stem cell research.
Dr. Richard Gatti, a professor of pathology and laboratory medicine, will receive $1,833,054 to use ataxia telangiectasia (A-T), an inherited neurodegenerative disease in children, as a model to study the mechanisms that lead to neurodegeneration. He will also develop a drug that can slow or halt such damage.
Dr. Thomas Carmichael, an associate professor of neurology, will also receive $1,825,613 to develop tissue bioengineering systems for a stem cell therapy to treat stroke. His research seeks to circumvent one major treatment bottleneck: the inability of most stem cell therapies to survive and repair the injured brain.
The grants were among 19 awarded Jan. 27 to researchers at 10 institutions by the California Institute for Regenerative Medicine (CIRM), the state agency that administers Proposition 71 funding for stem cell research. Part of the Tools and Technologies II Awards, the two-year grants support the development and evaluation of innovative tools and technologies that will help researchers overcome roadblocks in stem cell research. The awards were given to scientists to either create new tools and technologies or expand existing tools or technologies that have shown promise.
To date, scientists at the Broad Stem Cell Research Center have received 42 grants from CIRM totaling more than $138.8 million.
Dr. Richard Gatti
Gatti's project merges the expertise of two major research cultures. He has long-standing experience researching a treatment for A-T, and William Lowry, an assistant professor of molecular, cellular and developmental biology in the UCLA Division of Life Sciences, has had success in converting skin cells into pluripotent stem cells that are then differentiated into cells of the nervous system. Together they hope to develop a disease model system for A-T.
Gatti proposes to start with skin cells grown from biopsies of patients with A-T who carry mutations in the ataxia telangiectasia mutated (ATM) gene. He hopes to convert the skin cells into pluripotent stem cells capable of forming the neural cells lacking in A-T patients' brains. It is presumed that these neural cells need ATM protein to develop normally. Gatti will then test the efficacy of the most promising new compounds — which have been in development in his lab over the past six years — on those neural cells.
Currently, there is no other disease model, either in animals or a Petri dish, for evaluating the effects of potentially curative compounds on the nervous system and its development. There is no effective treatment for children with A-T or other progressively-deteriorating neural disorders. If successful, Gatti's project would open up at least three new areas for understanding and treating neurodegenerative diseases: providing human neural cells with specific disease-causing mutations; offering a new approach to learning how the human brain develops; and developing a new class of drugs that may correct the disease-causing mutations and possibly reverse neurodegeneration.
Dr. Thomas Carmichael
Stroke currently is the leading cause of adult disability. While most patients survive an initial stroke, they don't fully recover. Up to one-third of stroke patients end up in nursing homes or assisted living centers and experience decreased strength or lack of control of the arms or legs.
There is no treatment that promotes brain repair and recovery from stroke. While recent studies in animal models show that stem cell transplantation into the brain promotes repair and recovery, no such treatment is available for humans. Three challenges must first be overcome: most of the transplanted cells die; most of the surviving cells don't interact with the surrounding brain; and the process of injecting stem cells into the brain may damage the normal brain tissue near the stroke site.
Carmichael will assemble a investigative team and undertake a novel research approach to overcome these challenges. Combining the expertise of engineering, stem cell biology and stroke scientists, he hopes to develop systems to support stem cell therapy in stroke by creating a biopolymer hydrogel that can be injected along with stem cells into the brain to provide the cells with a pro-growth and pro-survival environment.
The hydrogel system uses biological components that mimic the normal brain environment and release growth factors that enhance survival of the transplanted stem cells. The growth factors, it is hoped, will stimulate the normal brain to undergo repair and recovery, providing a dual mechanism for repair. This approach allows targeting of the stroke cavity for a stem cell transplant. The cavity is an ideal target for stroke stem cell therapy, as it can receive a stem cell transplant without displacing the normal brain.
The Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research: UCLA's stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Broad Stem Cell Research Center is committed to a multidisciplinary, integrated collaboration among scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed toward future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine at UCLA, UCLA's Jonsson Cancer Center, the UCLA Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science.