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CIRM MAJOR FACILITIES GRANT APPLICATION #FA1-00620-1

Recommendation: Not recommended for further consideration
Element X Score: N/A
Element Y Score: —
Element Z Score: N/A
Use & Contribution Score:—

Public Abstract (provided by applicant)

The Proposed CIRM Major Facility The proposed facility will support the establishment of the Neurogenesis Institute of Stem Cell Technology on our campus. The scientists from relevant disciplines will use the facility to conduct research in drug discovery for Alzheimer’s disease using stem cells. We also plan to use the facility for advanced training of working professionals in stem cell technology and stem cell research lab management. The major facility will house labs for culturing and storing stem cells, producing drug-like compounds from natural plants, analyzing these compounds’ effect on stem cells and in the brain tissue. The research lab space will have an open layout with research bay areas shared by scientists and their students. This design will facilitate on-going interactions and exchange of results and ideas. The conference room will be used both as a meeting room and a small classroom for training purposes.

The Stem Cell Research Program Our goal is to find drug-like compounds in treating Alzheimer’s disease (AD) and other related diseases. AD is the most common neurodegenerative disease with a debilitating and fatal outcome that afflicts 15 million people worldwide. The geriatric demographic dictates an increase in this patient population to 45 million by 2050, with 16 million in the United States. In the absence of an effective treatment, the cost to society and the extent of human suffering are incalculable. The drugs for AD patients lose their effectiveness 2-3 years following diagnosis and do not treat the root cause of the disease. Stem cell therapies require direct delivery to the brain via surgery, which would be highly impractical and risk-ridden for this large elderly patient population. The ideal treatment for AD would be to orally administer a drug that can penetrate into the brain to stimulate the local stem cells to develop and proliferate into new and functional neurons. This approach would avoid brain surgery and offer hope for a preventative treatment of cognitive decline across the general population.

We will use a proven chemical conditioning process on natural plants to produce novel and drug-like compounds. These compounds will be screened using neural stem cells. Their effects on stem cells will be studied and the drug-target interactions analyzed. Finally, the drug-like compounds’ effect in the brain will be examined in preclinical studies. This program covers a broad scope of stem cell research as well as an in-depth pursuit of drug-like compounds in treating AD and related diseases.

The Benefits of the Major Facility Currently, we do not have a designated facility for stem cell research. Such a facility will allow scientists to work effectively to achieve the common goals of finding practical therapeutic cures for AD and other related diseases. The advanced training in evenings and weekends will produce master’s level stem cell technologists that are much needed to support stem cell scientists in CA.

Statement of Benefit to California (provided by applicant)

The Proposed Facility and the Stem Cell Program The facility will house a set of labs with open layout to facilitate on-going interactions and exchange of results and ideas. The facility will be used for dual purposes. 1) For research, we will use a proven chemical conditioning process to produce drug-like compounds from plant extracts. The compounds will be screened and their effects on cellular development and aging will be studies using neural and embryonic stem cells. Further drug-target interactions and the drug effects will be carried out in preclinical studies. This program covers a broad scope of stem cell research with a specific focus and an in-depth pursuit of drug-like compounds in treating Alzheimer’s (AD) and related diseases. 2) For training, we plan to add to our existing successful professional science master’s degree in biotechnology/MBA with specially tailored courses in advanced stem cell techniques and stem cell lab management. These classes will be offered in the facility evenings and weekends to train working professionals at the master level so that they could provide much needed support to the senior scientists in stem cell research field.

The Benefits of the Major Facility and the Stem Cell Program to California AD is the most common neurodegenerative disease with a debilitating and fatal outcome that afflicts 15 million people worldwide. Over 500,000 Californians are affected by this illness, with the most conservative estimation predicting the population to reach 1.6 million in California by 2050. The cost to the State and local governments, the extent of human suffering, and the loss of productivity due to family members providing long-term care to their afflicted loved ones are immeasurable. Current drugs for AD become ineffective after 2-3 years and they do not provide a cure. Stem cell therapy requires brain surgery to deliver stem cells into a large patient population, which is impractical, costly and risk-ridden. Our research is to find drugs that can be formulated for oral intake, a therapeutic approach that is innovative, practical and economical. We have received over $2 million in donations from the private sector to support our endeavors and we have sufficient matching fund required by this grant. The proposed facility will allow scientists to work effectively to achieve the common goal of finding cures for AD and other related diseases. Our research results will lead to discovery of effective drugs in treating AD patients for which thousands of Californians will benefit. The State of California does not have a program to provide advanced training in stem cell technology and stem cell lab management. However, the need in specially trained personnel is staggering in support of the $3 billion Stem Cell Initiative in the State. Our training program will produce much needed professionals at the master’s level to join the scientific workforce in stem cell research in California.

Review Report

Executive Summary

This is an application for a facility to support a preclinical research program that will focus on screening molecules for potential drug development for Alzheimer’s disease. The facility will also be used for training in stem cell technology. The facility will house labs for culturing and storing stem cells and for producing natural products from plants. The research approach will screen neural stem cells to screen for bioactive components in extracts derived from natural sources using a proven extraction process and a variety of assays .

Overall, this proposed research program appears very focused on one approach to developing compounds for Alzheimer’s disease. Reviewers felt that the strength of this application is the novel extraction regimen for natural products as a source of new compounds that would be used for screening. However, there is relatively little evidence of expertise in stem cell culturing and manipulation and the scientific environment lacks depth and breadth. The plans for growth are vague and include plans to add faculty in many basic research areas not specifically linked to this stem cell proposal. The core facilities are not well described. The scientific environment needs to be strengthened and plans for hiring new faculty are poorly defined.

Detailed Summary

Element Y

Score: —

SCIENTIFIC PROGRAM: This is a new university that was established just a few years ago and houses an institute dedicated to research on Alzheimer’s disease. The institute is headed by a medicinal chemist who previously was at a biotech company. The university has obtained support for general infrastructure and facilities, a part of which would be used as matching funds for this grant.

The director of the institute has nine years of industry experience in small molecule drug discovery. The applicant organization currently has two chemists and two biologists with some experience in stem cell research. The plans are to have five PIs, one medicinal chemist, one molecular biologist, one immunologist, one structural biochemist, and one neuroscientist. The biologists in particular are to have a background in stem cell biology and technology. The new institute hopes to continue to expand to hold three additional biologists to strengthen and complement the initial five.

The long term goals of the program include the establishment of an institute to conduct interdisciplinary research in small molecule drug discovery for Alzheimer’s disease using stem cells and training of personnel in stem cell technology and stem cell research laboratory management. There is relatively little evidence of any expertise in stem cell culturing and manipulation and the scientific environment lacks depth and breadth.

The proposed training aspects of their new program would be within the existing framework of their current masters program in biotechnology and they plan to add classes in stem cell techniques and lab management in the evenings and weekends to train additional research technicians to support senior scientists in their stem cell research laboratories. The applicants emphasize that this would further support the California stem cell initiative by supplying trained technicians. The strength is that the existing infrastructure already exists.

FORMAL INSTITUTIONAL COLLABORATIONS: Scientists at the applicant institution have established two scientific collaborations with neural stem cell researchers at two California institutions. One is a neuroscientist and has been providing advice as an advisory board member. The other has been collaborating with institute’s director for two years. Two letters of collaboration were included. No specific details are provided.

CORE SERVICES: A number of cores not to be housed in the new facility are described. Cores to be located in the new facility include image analysis, tissue culture, cell sorting, common equipment and a vivarium. Details of the cores and the management/business plans are lacking. There is currently no existing space for stem cell research, hiring additional faculty, or for additional equipment. The proposed facility will house two molecular biology labs for 5 PIs in the near term and will house 8 PIs in the long term.

PLANS FOR GROWTH: The applicant institution plans to build another science building on the campus in the next 5-7 years and would have additional research lab space in the new building. It is forward thinking that they are planning for further growth. They intend to hire a neuroscientist with stem cell experience. There is a statement without details on hiring future faculty members in genetics, neurophysiology, cell biology, physical chemistry and bioinformatics.

DISCUSSION: The scientific program focus is on stem cells and Alzheimer’s disease, plus a training program for stem cell culture, and for stem cell research lab management. However, reviewers felt it was not clear that the applicants had any expertise in the area of stem cell research. They propose many things with not much detail about how they will be implemented. The application is very focused on one disease and one technology, but it is not clear how it will work. The focus on one disease was cited as a potential strength by one reviewer but the lack of stem cell expertise was a significant weakness. The institution is just beginning work in hESCs and investigators have not established themselves as researchers, as evidenced by the absence of NIH grants. Reviewers expressed concern in this regard.

One reviewer felt that the proposal might be viewed as a start-up grant application, but that it is not appropriate for a facility award.

Use & Contribution

Score: —

The proposed facility will support establishment of preclinical stem cell research program with a focus on Alzheimer’s disease. The facility will house wet labs, shared equipment and some core services. The laboratories will be an open configuration. About sixty percent of the total space planned is assignable to labs, core facilities and office/administrative support. About 50% of this space will be used as common space. The plan is for the space to house 5 investigators. There was no specific plan to encourage interactions other than by physical proximity. There is currently no designated space on this campus for research on non-Federally approved cell lines, but there has been no Federal money utilized in construction of the spaces on the campus to date.

The following Working Group members had a conflict of interest with this application and were therefore recused from participating in review of, discussion of, and voting on the application:

• Feit, Marcy