Funding opportunities

Executive Summary This applicant proposes to organize a team that will focus on developing novel cellular therapies to improve the quality of life for individuals afflicted with spinal cord injury (SCI). The proposed planning team will include SCI researchers, stem cell biologists, and bioengineers from a number of California institutions to evaluate the utility of different glial cell progenitors for clinical use. Expert consultants will be brought in to help lead workshops aimed at clearly defining the targets and strategies for SC based therapies for SCI. SCI is an obvious area of significant unmet medical need. Spinal cord injuries affect 10-12,000 new individuals in the United States each year, and 250,000 Americans suffer chronically from the disease. The case to develop novel cellular therapies to improve the quality of life for individuals afflicted with spinal cord injury is thus well-justified and compelling. Unfortunately, reviewers found that this particular disease team planning application is not very strong. The applicant has very thinly put together a disease team, the proposal lacks definition, and the planning process is not well organized. The proposed planning approach includes a 3-step process, first to identify key players and identify the goal, second to organize working groups with team members and consultants to break down the goal into a series of milestone-defined decision points based on gaps and roadblocks, and finally to put the grant proposal together. The applicant did not adequately discuss a translational timeline and which team members (or what type of team members) would be involved in each phase of the project. In addition, reviewers commented that this consortium will not be in a position to address all the variables experimentally, and the planning process does not discuss how well-considered, at times hard decisions, will be made. Reviewers felt that this is a complex proposal and were uncertain that the concept could be clinic-ready in the 5 year time-frame required by this RFA. There are a large number of scientific variables that must be considered in the design of a clinical study for the treatment of SCI. The PI rightly includes variables such as determining which cells should be used, defining the best approach to control other tissue microenvironment at the site of the lesion, and determining whether large animal studies can be performed. These are very big questions, and reviewers were concerned that the planning process proposed did not outline how these decisions could be reached with such a diverse group of high-profile investigators. The strengths of the proposal are the people involved. Importantly the principal investigator (PI) is a seasoned research team leader with years of experience in developing preclinical SCI models and rodents. The Co-PI is a prominent, NIH-funded M.D/Ph.D neurosurgeon with basic science, clinical trials and therapeutic development experience in neurotrauma. These two individuals will serve as excellent team leaders for a project in SCI. The strong spirit of collaborative basic and clinical research around SCI in California is noted and will greatly facilitate the planning process. The weaknesses identified above, however, reduced the reviewers’ enthusiasm for this grant. Reviewer One Comments Importantly the PI of this disease planning meeting is a seasoned research team leader with years of experience in developing preclinical spinal cord models and rodents. In addition, the Co-PI is a prominent, NIH-funded M.D/Ph.D neurosurgeon with both basic science, clinical trials and therapeutic development experience in neurotrauma. These two individuals will serve as excellent team leaders for this planning grant. The planning approach includes a 3-step process, first to identify key players and agreeing on a clear goal to tackle, second to organize various working groups to meet with consultants to break down the goal into a series of milestone-based decision points based on gaps and roadblocks, and eventually to put the grant proposal together. Overall this is a well-described proposal and identifies Co-PI and PI as well as a number of others in the California system who have experience including doctors Basbaum, Bresnahan, Kriegstein, Nobile and Pleasure. The applicants have identified organizations that will be used to help in the planning process, including the American clinical trials network for spinal cord injury. Overall this is a nicely designed grant proposal which perhaps could be further improved if they had spent a little more time identifying individuals within each of the stages that would be helped form this disease planning team. Although enthusiasm for the proposal is high, it is slightly offset by this lack of consideration of description of a more defined proposal with identified individuals. Reviewer Two Comments Concept: The case to develop novel cellular therapies to improve the quality of life for individuals afflicted with spinal cord injury is well justified and indeed, compelling. SCI is an obvious area of significant unmet medical need. There are a large number of important variables that must be considered in the design of a clinical study for the treatment of SCI. The PI has done a very good job listing these and rightly includes variables such as: a) which cells should be used, b) what is the best approach to control other tissue microenvironment at the site of the lesion, and c) whether large animal studies should be performed. These are very big questions and a concern is whether consensus amongst the proposed disease team be reached and how quickly will that occur. This is a complex proposal, and it is uncertain that it will make it in the time-frame of 5-6 years. Principal Investigator: The pairing of the PI (Dr Beattie) with Co-PI (Dr Manley) as “leaders among equals” is ideal. Their collective experience and track records in the field are key to this progressing to the stage of submitting a full proposal. Planning Approach: The strong spirit of collaborative basic and clinical research around SCI in California is noted and will greatly facilitate the planning process. The steps outlined seem very appropriate and address key issues in moving SCI therapies to the point of clinical application. As noted above, however, some key decisions will have to be made early on in these deliberations (which cells, animal model, conditioning, lesion microenvironment, etc.,). This consortium will not be in a position to address all the variables experimentally and it is essential that well-considered, at times hard decisions are made.