Armin Blesch, Ph.D.
Associate Professor

Current Research

Spatial gradients of axonal growth factors
Continuing studies are examining effects of neurotrophic factors on axonal regeneration after spinal cord injury (SCI). Previous studies have shown that delivery of neurotrophic factors at sites of SCI strongly enhances the number of axons growing into a lesion site but axons rarely extend beyond sites of SCI. Current experiments are examining whether gradients of neurotrophic factors established by viral gene transfer at and beyond sites of SCI can induce axons to bridge across a site of SCI filled with a cellular graft.

Regulated gene transfer in the central nervous system
Exogenous regulation of gene expression is a desirable property to enhance the safety of gene therapy and to maximize cellular responses to neuroprotective or axon growth promoting molecules. Tetracycline-responsive promoters are one possibility in this regard and our studies have indicated that the expression of neurotrophic factors, or a reporter gene, can be regulated in vitro and in vivo allowing for regulation of biological responses such as axonal growth and neuronal survival. Continuing studies are examining whether transient, regulated neurotrophin delivery is sufficient to induce axonal growth and to sustain axons once they have regenerated.

Combinatorial therapies for spinal cord injury
In collaboration with Dr. Mark Tuszynski and Dr. Paul Lu, we are investigating whether combination of neurotrophic factors with other axon promoting stimuli such as increases in cAMP levels can enhance the number and distance of regenerating axons.

Expression of green fluorescent protein after injection of lentivirus into the adult spinal cord. Click to view complete figure in a new window.

Genetic programs for axonal regeneration
Regeneration in the peripheral nervous system is vastly superior compared to regeneration in the central nervous system. It is known that regenerative programs in peripheral dorsal root ganglion neurons are tightly controlled by defined changes in gene expression. Using microarray analysis, in vitro studies and lentiviral gene transfer we aim to identify important regulators of these genetic programs. Once identified, these genes can be used to enhance regenerative responses of CNS neurons.

Gene therapy in neurodegenerative disorders, aging and stroke
In several collaborative studies we are investigating whether gene delivery of potentially therapeutic proteins and growth factors to the central nervous system can prevent neuronal degeneration in anima models of stroke, Alzheimer's disease and Parkinson's disease.



Recent Publications

Blesch A, Tuszynski MH. Transient growth factor delivery retains regenerated axons after spinal cord injury. Journal of Neuroscience (2007) : in press

Taylor L, Jones L, Tuszynski MH, Blesch A. NT-3 gradients established by lentiviral gene transfer promote short-distance axonal bridging into and beyond cellular grafts in the injured spinal cord. Journal of Neuroscience (2006): 26: 9713-9721.

Blesch A. Neurotrophic factors in neurodegeneration. Brain Pathology (2006): 16:295-303.

Blesch A. Neurotrophin gene therapy for Alzheimer's disease. Future Neurology (2006): 1: 179-187.

Alfa RW and Blesch A. Murine and HIV-based retroviral vectors for in vitro and in vivo gene transfer. Wang Q (ed.): Methods in Molecular Medicine: Cardiovascular Disease: Methods and Protocols (2006): 129:241-254.

Vroemen M, Weidner N and Blesch A. Loss of gene expression in lentivirus- and retrovirus- transduced neural progenitor cells is correlated to migration and differentiation in the adult spinal cord: Experimental Neurology (2005): 195:127-139.

Tuszynski MH, Thal L, Pay M, Salmon D, U H-S, Bakay R, Blesch A, Vahlsing L, Ho G, Tong G, Potkin S, Fallon J, Mufson E, Kordower J, Gall C, Conner J. A phase I clinical trial of nerve growth factor gene therapy for Alzheimer's disease. Nature Medicine (2005): 11:551-555.

Blesch A, Conner J, Pfeiffer A, Gasmi M, Britton W, Alfa R, Verma I, Tuszynski MH. Regulated lentiviral NGF gene transfer controls rescue of medial septal cholinergic neurons. Molecular Therapy (2005): 11: 916-925.

Blesch A. MLV based retroviral and lentiviral vectors for in vitro and in vivo gene transfer. Methods (2004): 33:164-172.

Tuszynski MH, Blesch A. Nerve growth factor: from animal models of cholinergic neuronal degeneration to gene therapy in Alzheimer's disease. Progress in Brain Research (2004): 146:441-449.

Blesch A, Yang H, Weidner N, Hoang A, Otero D. Axonal responses to cellularly delivered NT-4/5 after spinal cord injury. Molecular and Cellular Neuroscience (2004): 27: 190-201.

Blesch A, Tuszynski MH. Cellular GDNF delivery promotes growth of motor and dorsal column sensory axons after partial and complete spinal cord transections, and induces remyelination. Journal of Comparative Neurology (2003): 467:403-417.

Blesch A, Tuszynski MH. Spontaneous and neurotrophin induced plasticity after spinal cord injury. Progress in Brain Research (2002): 137: 415-423.

Tuszynski MH, Grill RJ, Jones LL, McKay HM, Blesch A. Spontaneous and augmented growth of axons in the primate spinal cord: effects of local injury and nerve growth factor-secreting cell grafts. Journal of Comparative Neurology (2002): 449:88-101.