SBIR-STTR Award

Neuronal replacement therapy is a promising approach for the treatment of spinal cord injury. The unique properties of hNT-Neurons make tem a potential source of cells for this purpose. hNT-Neurons are pure, post-mitotic, differentiated human neuronal cells that can be produced in unlimited quantities according to Good Manufacturing Practices. In transplantation experiments, these neurons survive, mature, grow neurites, form synapses, integrate, and restore functioning. The proposed research is bas4ed on an appreciation of the plasticity of the neurons and their diverse neurotransmitter phenotypes, important properties for the development of optimal spinal cord replacement neurons. The aims are to vary the parameters of the differentiation process to produce hNT-Neurons with selected phenotypes, screen the activity of specific neuronal preparations in spinal cord explant cultures in vitro, and evaluate the optimized hNT-Neurons in an animal model of spinal cord injury in vivo. Preliminary evidence suggests that hNT-Neurons are scientifically promising, technically feasible, and commercially viable as a source of replacement neurons for the treatment of spinal cord injury and other CNS disorders

hNT-Neurons are pure human neuronal cells that exhibit neuronal phenotypes and efficiently engraft following transplantation into rodent spinal cord. Phase I studies successfully developed hNT-Neurons with properties suitable for spinal cord transplantation, identified the critical experimental conditions to maximize graft success in vivo, and demonstrated graft survival in a rodent model of clinically relevant cervical spinal cord contusion injury. Phase II studies will focus on further product development, optimization of grafting protocols, and intensive anatomical, neurophysiological and behavioral studies of long-term safety and efficacy. Specific aims include: (1) examine graft survival, rate of cellular differentiation, neurotransmitter phenotypic profiles, and neuritic outgrowth as a function of the cell density of grafted hNT-Neurons; and (2) establish long-term safety and functional efficacy by monitoring the safety profile, phrenic motoneuron function, and forelimb motor behavior over extended time periods following grafts of hNT-Neurons in spinal cord contusion injury. The results of these experiments will help establish the therapeutic potential of hNT-Neurons to improve outcomes in spinal cord injury and provide valuable information necessary to move ahead toward clinical trials.