Human stem cells have the demonstrated ability to differentiate into a variety of specific cell types. This has generated widespread hope that these cells may be a resource for replacing damaged or deteriorating tissues in patients. However the process of directing stem cell fate toward a beneficial cell type is inefficient. Therefore considerable research is needed to identify and develop compounds, representing new drug candidates, that reliably direct stem cells to desired cell types with regenerative capabilities. Initial ‘hit’ compounds identified through various research approaches typically are not very ‘drug-like’. It’s expected that large numbers of compounds closely related to the initial ‘hit’ must be synthesized and evaluated for improved efficacy and safety before testing in humans is possible. These drug candidates, identified by their ability to positively direct stem cell fate, will require a thorough characterization with regard to their structure, metabolism, and safety. Coordinating the many steps in the process of drug development, from stem cells to testing compounds in animals, would be optimized by housing these activities in one facility. To address the challenge of translating stem cell research into novel therapeutics, we will establish a new facility for medicinal chemistry and preclinical safety evaluation of drug candidates. We will make available to other CIRM investigators its expertise in the areas of stem cell biology, chemical synthesis and analysis, metabolic studies, and safety evaluation of compounds in animals. The new facility housing these activities will be created through renovation of existing space adjacent to our current Institute, to be divided between new laboratory and administrative areas. The proposed Drug Development Center will support an expanded research and technical staff, contributing to the stem cell initiative through both internal projects as well as ongoing and new collaborations. Six administrative units will be established for managing the research programs. These units will be complementary, and will provide competencies in all steps of the drug development process. The new facility will support our current CIRM funded efforts using stem cells to develop novel therapeutics for heart disease, a leading cause of mortality and decline in quality of life in the developed world. Similarly, through collaborations with other CIRM investigators the new facility will support drug development efforts in many other disease areas. Our institute has extensive experience with investigational new drug (IND) preparation and new drug applications (NDAs), and today many of those drug candidates are new drugs on the market. The new Drug Development Center will benefit greatly from this experience. By bringing new investigators and a collaborative approach to the stem cell field, this facility responds directly to the CIRM initiative to deliver new therapeutics based on stem cell research.
Statement of Benefit to California:
Millions of people currently suffer from devastating diseases or injuries that are currently incurable, including cancer, heart disease, Alzheimer’s, spinal cord injuries, and many others. Long-term health care places a heavy burden on patients, their families, and the state health care system. The ability of human stem cells to differentiate into specific cell types has generated enthusiasm that these cells may be a resource for replacing damaged or deteriorating tissues in patients. However the process of directing stem cell determination is inefficient, largely due to an incomplete understanding of the inducing signals and pathways involved. Various technical approaches lead to identification of ‘hit’ compounds with the potential to direct stem cells toward desired cell types, but which frequently have limited efficacy or stability. The drug development process typically requires subsequent chemical synthesis of large numbers of drug-like analogs, and thorough characterization with regard to their metabolism, selectivity, and safety. The California stem cell and regenerative medicine initiative will require a comprehensive program of research, analytical, and preclinical safety evaluation before drug candidates can be tested in a clinical setting. To address the challenge of translating basic stem cell research into effective therapies, we will establish a new facility for medicinal chemistry and preclinical analysis of lead compounds and optimized drug candidates. The proposed Drug Development Center will support our current CIRM funded efforts to develop potent and selective drug-like molecules to direct stem cell cardiomyogenesis for treatment of heart disease. Coordinating the various steps in preclinical drug development in one facility will offer advantages in efficiency, time, and cost. Through collaborations, other CIRM investigators will similarly benefit by access to our preclinical services in the areas of stem cell biology, chemical synthesis and analysis, ADMET screening, and safety evaluation of lead compounds in vitro and in animals. These collaborations will enhance opportunities for developing effective new therapeutics in many other areas of disease research. By bringing new investigators and collaborative approaches to the stem cell field, the proposed new facility will respond directly to the CIRM initiative by accelerating development of new therapies for potentially millions of Californians suffering from chronic illnesses and injuries. Patients and their families will benefit, in terms of improved quality of life and reduced financial burden, from treatments that will derive from the proposed stem cell and drug development efforts. Also, benefits to the California health care system will ultimately be realized by switching focus from the maintenance of chronic conditions to prevention and cures.