Transplantation & Regeneration
Various cell types or bridging strategies have been evaluated by the Miami Project as well as by other centers throughout the world targeting SCI. Both adult and embryonic stem cells have been shown to enhance recovery in some preclinical models of SCI and continue to be a research focus. Various bridging strategies including the use of biological and acellular grafts show promise in terms of helping axons grow across injury-induced gaps in the spinal cord. The addition of growth promoting factors either through infusions of proteins or gene therapy is a powerful and exciting method in which to target both the intrinsic as well as extrinsic mechanisms of axonal regeneration. Indeed, high content screening strategies as well as other molecular approaches are identifying novel genes and proteins that can enhance neurite growth, promote new vessel formation and successful regeneration in models of SCI and TBI. Thus, it is clear that major strides have been made regarding what regenerative strategies including cellular transplantation should be considered as we test and attempt to translate our findings.
The Miami Project made an informed decision several years ago to concentrate on the human Schwann cell as a means to promote repair in the acute and chronically injured spinal cord. Based on studies from both small and large animals, Schwann cell transplantation was reported to be safe and effective in improving functional outcome in these clinically relevant animal models. The ability to use an individual’s own Schwann cells and inject them autologously is believed to be a major advantage as we try to move these new therapies to people. In addition, to enhance cell survival after transplantation and obtain FDA approval for clinical studies, good manufacturing procedures and cell processing strategies have been established to ensure that cells that are injected are healthy and will function in a hostile environment of the injured spinal cord. Schwann cells release a variety of growth-promoting factors as well as have the capacity to remyelinate (insulate) injured fibers that we believe will help lead to increased axonal function in lesions where axons are intact but demyelinated. The use of cutting-edge viral vector technology has also now permitted the continuous visualization of the transplanted cells for weeks to months to evaluate migration tendencies and assess long term survival.
Based on years of research and published studies, an Investigational New Drug Application (IND) was approved by the FDA in 2012 for the use of autologous Schwann cell transplantation to target injured individuals with subacute severe spinal cord injury; several subjects have already been successfully transplanted. The long term monitoring of these individuals will continue over the next few years as we continue to recruit additional subjects for this initial dose escalation safety study. Because of the overall goal of the Miami Project to develop new therapies for people today living with spinal cord injury, addendums and new clinical protocols are being proposed and submitted where Schwann cell transplantation will be initiated in chronically injured subjects to target the larger population of people living today with SCI. In these studies additional programs such as the Boot Camp will be combined with the transplantations procedures. Also, subsequent programs will combine Schwann cell transplantation with other treatments that may enhance the ability of this cellular therapy to promote significant recovery in the chronic situation. It’s a truly special feeling for medical researchers to see their research discoveries translated to the SCI community. This important FDA approved trial represents an important step in our goal to develop new therapies to improve function and quality of life for the SCI community.