The goal of this project is to produce a stem cell-based therapy for stroke (also known as an ischemic cerebral infarct). Stroke is the third leading cause of death in the USA, and a leading cause of disability among adults. Currently, there are no effective treatments once a stroke has occurred (termed completed stroke). In this proposal, we aim to develop human stem cells for therapeutic transplantation to treat stroke. Potential benefits will outweigh risks because only patients with severe strokes that have compromised activities of daily living to an extreme degree will initially be treated. Using a novel approach, we will generate stem cells that do not form tumors, but instead only make new nerve cells. We will give drugs to avoid rejection of the transplanted cells. Thus, the treatment should be safe. We will first test the cells in stroke models in rodents (mice and rats) in preparation for a human clinical trial. We will collect comprehensive data on the mice and rats to determine if the stem cells indeed become new nerve cells to replace the damaged tissue and to assess if the behavior of the mice and rats has improved. If successfully developed and commercialized, this approach has the potential for revolutionizing stroke therapy.
The goal of this project is to produce a stem cell-based therapy for stroke (also known as an ischemic cerebral infarct). Stroke is the third leading cause of death in the State of California, and a leading cause of disability among adults. Currently, there are no effective treatments once a stroke has occurred (termed completed stroke), and the quality of life is severely compromised in those that survive the malady. In this proposal, we aim to develop human stem cells for therapeutic transplantation to treat stroke. Using a novel approach, we will generate stem cells that do not form tumors, but instead only make new nerve cells. If successfully developed and commercialized, this approach could provide a therapeutic candidate for the unmet medical need, which would have a tremendous impact on the quality of life for the patient, his or her family, and for the economic and emotional burden on the State of California and its citizens.
This application for a Development Candidate Feasibility (DCF) award is focused on a stem cell-based therapy for stroke. The applicant proposes to genetically engineer neural stem cells (NSCs) derived from human embryonic stem cells and test their functionality in an animal model of stroke. The project milestones include cell production, optimization of cell dose and transplantation regimens, as well as comprehensive analysis of transplanted animals.
Objective and Milestones
- The target product profile (TPP) is scientifically and clinically reasonable. Reviewers appreciated that it specifies inclusion criteria, acknowledging that not all stroke patients will be candidates for this type of therapy.
- The milestones should be rewritten with go/no go decision points and clearly defined success criteria.
- The transplantation procedure and delivery system envisioned for clinical application is not described.
Rationale and Significance
- Stroke is a common cause of death and disability with very few treatment options available.
- A number of adult cell therapies are already in Phase 2 clinical trials. If any of these show benefit, the bar will be set higher for this proposed, potentially riskier approach.
Feasibility and Design
- The research plan is logically written and takes a sequential, step-wise approach. Potential pitfalls and alternative approaches are well described.
- The preliminary data are supportive of the approach, although not compelling. Reviewers did appreciate that the applicant performed behavioral assays prior to transplant in order to establish a baseline for comparison.
- Reviewers would have appreciated more quantitative data regarding cell differentiation following transplantation.
- Immunosuppression was mentioned, but insufficient detail was provided.
- Reviewers questioned the use of infarct volume as an efficacy endpoint for this approach. They also would have appreciated details about plans for seizure monitoring.
Qualification of the PI (Co-PI, Partner PI, if applicable) and Research Team
- The PI has an outstanding track record and has assembled an excellent team.
Collaborations, Assets, Resources and Environment
- Institutional support is sufficient to complete the proposed work.
Responsiveness to the RFA
- The proposal is responsive to the RFA.