Collaboration
To help accelerate therapies from laboratory to clinical trial, the W. M. Keck Center for Collaborative Neuroscience provides several critical services for the field. First, we provide and train people to use the IMPACTOR model of rat spinal cord contusion. Second, we developed and provide the first large-scale and low-cost rat gene chips for SCI research. Third, we are providing stem cells and other cells for transplantation. Fourth, we hold 4 workshops training 60-80 people per year to use the IMPACTOR, do SCI research, and apply the gene chips. Over the past three years, we have trained over 100 laboratories to do SCI research, to do gene expression analyses, and to carry out and evaluate cell transplants and Regeneration. Each of these services are described below.
• The IMPACTOR. This device is sometimes called the NYU Impactor because it was originally developed at NYU Medical Center. This device precisely monitors and delivers a transient mechanical compression of the rat spinal cord. In addition to controlling and measuring the mechanical perturbation of the spinal cord precisely, the model standardized anesthesia, pre- and post-injury care, and outcome measures. The first well-accepted and standardized rat locomotion scale (the BBB score) was developed for this model. This scale allows locomotor recovery to be quantified reliably. The IMPACTOR model is currently used by about 150 laboratories around the world.
• Gene Chips. The Neuroscience Gene Expression Laboratory (NGEL) at the W. M. Keck Center for Collaborative Neuroscience developed two rat gene chips. These chips are glass slides spotted with 5000-10,000 genes. To use the chips, one isolates messenger RNA from tissues, label the RNA with fluorescent tags, and then apply the RNA to the chips. The RNA binds to the DNA spots and the level of fluorescence reflect the amount of RNA expressed by that gene in the tissue. The first chip or NGEL 1.0 is a cDNA chip which has 10,000 genes, half of which are known. The second chip or NGEL 2.0 has 5000 identified genes and uses 70-80 mer synthetic nucleotides that are highly specific. These chips will allow discovery of new genes that may play a role in injury, repair, and regeneration of the spinal cord, as well as pain and Spasticity. The chips allow treatments to be evaluated quickly and efficiently in rats.
• Cell Bank. Most SCI researchers do not have ready access to rat stem cells. They must establish their own cell culture laboratories and hire people to prepare stem cells and other cell lines for treatment of spinal cord injury. We have a transgenic rat that expresses the green fluorescent protein (GFP) in virtually all cells of the body. When transplanted, these cells can be visualized in tissues without staining. We are establishing a cell bank of well-characterized rat stem and other cell lines that researchers can implant into rat spinal cord without immunosuppression. These include embryonic stem cells, fetal stem cells, neuronally restricted precursors (NRPs), glial restricted precursors (GRPs), oligodendroglial precursors, and olfactory ensheathing glia. Having a standardized and well-characterized source of cells not only saves time and money but also allows laboratories to compare results.
The W. M. Keck Center for Collaborative Neuroscience is offering these three services at cost to collaborators. For example, we provide the IMPACTOR for about $6000 which is the cost of manufacturing and servicing the device, the NGEL chips at $100 each (compared to >$1000 cost of commercial chips), and cell lines for the cost of storage, preparation, and shipping. We train people to use the model, the gene chip, and the cell transplants. These services should substantially reduce the cost and increase efficiency of SCI research. We offer these services to collaborating laboratories with one condition, that the data must be shared with other collaborators. The data are stored on two databases: the NGEL database for gene expression data and the SCICure database for injury parameters, treatments, and outcomes. Collaborators who contribute data will have access to both databases. No such databases are currently available.
A consortium of laboratories that share data has major advantages over the current laissez faire approach where scientists are finding out about results at annual meetings or journals. First, the data will be current, without the 6-8 month delay of journal publications and meetings. Second, laboratories will be able to learn about mistakes from each other so that they do not have to reinvent the wheel. Third, laboratories will be able to find out about negative results, i.e. treatments, doses, or approaches that do not work. Most laboratories do not rapidly report mistakes or treatments that do not work. Fourth, sharing data will allow more rapid consensus concerning the efficacy and safety of therapies for clinical trials. Fifth, the data can be used for meta-analyses, i.e. pooling data together from a series of smaller studies to come out with more convincing trends and . Collaboration will accelerate movement of therapies to clinical trial.
Conclusions
1. Grants. Most research grants pay for the direct costs of the research and indirect costs. The latter are the institutional costs of the research and are often 50-60% of direct cost. The National Institutes of Health (NIH) is the major government agency funding spinal cord injury research. NIH may fund fellowships that are about $100,000 per year for 3-5 years, individual research grants for $250,000 per year for 3-5 years, and program grants that may be as much as $1,000,000 per year for 3-5 years. State, industry, and private grants are smaller, on the order of $50,000-$100,000 per year for 1-2 years. An investigator who receives $500,000 per year of direct and indirect costs would be considered well-funded.
2. Budgets. Direct costs include personnel, equipment, supplies, communication, and other costs. Personnel costs include salary and fringe benefits that are typically 25% of salaries. An active laboratory headed by principal investigator usually includes a postdoctoral fellow, a technician, and a graduate student, costing about $190,000 per year. Most laboratories need about $500,000 of equipment in order to carry out SCI research. Assuming that all the equipment is already available, the laboratory will still need about $35,000 per year to upgrade the hardware and software. Supplies for 120 experiments per year average about $75,000 per year. Communications may cost $10,000 per year. Animal and care costs, and service contracts, will cost about $50,000. This direct cost budget of about $360,000 plus an indirect cost of $240,000 add up to over $500,000 per year, suggesting a cost of $4000-$5000 per experiment.
3. Funding. In 2000, the United States invested about $100 million into SCI research, compared to $60 million in 1995. If each laboratory requires about $500,000 and has about 1.5 full-time-equivalent scientists working, this suggests that $80 million can support about 160 SCI laboratories and perhaps 240 SCI scientists. In 2000, 1430 SCI papers were published with 33% animal studies and 37% from the U.S. In 1995, a total of 1049 SCI papers were published with 24% animal studies and 34% from the U.S. The number of U.S. animal SCI studies doubled from 109 to 218 between 1995 and 2000. However, US clinical SCI studies fell, especially in 1996-97. U.S. scientists and clinicians accounted for 37% of SCI studies and nearly half SCI animal studies in the world in 2000.
4. Research. Funding is a critical bottleneck to SCI research. Despite an overall increase of NIH funding over the past year and increasing interest by industry in funding clinical trials, the total US investment in SCI research is still about $100 million. There are not enough SCI scientists successfully competing for NIH funding. Thus, one strategy is to train more laboratories to do better SCI research. State and private foundation support is very helpful in helping nurture new laboratories to the point where they can compete for NIH funding. A second strategy is to improve the efficiency and productivity of researchers in the field. Because SCI studies are so laborious and time-consuming, providing resources so that individual laboratories do not have to reinvent the wheel, using gene expression as a surrogate measure of therapeutic effects, and forming consortia to share data should accelerate the pace of research. Finally, having a well-organized clinical trial infrastructure will reduce the delay in moving therapies from laboratory to clinical trial.
5. Collaboration. We have attempted to address some of the above obstacles systematically at the W. M. Keck Center for Collaborative Neuroscience. Over the past three years, we have trained over 100 laboratories to use the IMPACTOR, a well-standardized and reliable rat spinal cord injury model that allows investigators all over the world to compare results. We developed the first affordable large-scale rat gene chip to assess injury mechanisms and outcomes. We are developing and will provide green fluorescent protein rat stem cells and other cell lines for transplantation. These cells will reduce the work that laboratories must do to evaluate cell transplants and the cells will standardize transplantation therapy so that results can be compared across laboratories and time. Finally, we are developing a consortium of scientists, clinicians, industry, and members of the SCI community to share data and collaborate.
In summary, SCI research is very laborious, time-consuming, and consequently expensive. Although funding of SCI research has steadily increased over the past five years, with a corresponding increase in the number of studies and therapies being studied, the pace of research can be accelerated with more funding and resources. More and better SCI scientists are required to compete for NIH funds. More reliable SCI models and data-sharing should increase the efficiency and productivity of laboratories. A clinical trial network should reduce some of the delays in moving therapies from laboratory to clinical trial. At Rutgers, we have tried to address some of these problems with novel programs to train more laboratories to do SCI research, to provide state-of-the-art molecular and cellular tools that improve the efficiency and productivity of SCI research, and to promote data-sharing and collaboration in the field.
Source:http://carecure.org/
