Sangamo BioSciences, Inc. has announced the presentation of preclinical data from its ZFP Therapeutic™ program in nerve regeneration at the Fourteenth Annual Conference of the American Society for Neural Therapy and Repair.
The data generated, in a model of spinal cord injury (SCI), demonstrate that treatment of the spinal cord at the time of injury with a VEGF ZFP TF had a statistically significant effect on recovery of hind-limb function as well as a number of other measures of nerve integrity and health.
The work was carried out in the laboratory of Dr. Michael Fehlings who holds the Krembil Chair in Neural Repair and Regeneration at the Krembil Neuroscience Center, Toronto Western Hospital and the Division of Neurosurgery, Faculty of Medicine, University of Toronto, Ontario, Canada.
Dr. Fehlings is a Christopher Reeve Foundation Scientific Advisory Council member and a leading expert in the molecular mechanisms and treatment of SCI.
In collaboration with Dr. Fehlings and his colleagues, Sangamo is evaluating a zinc finger DNA-binding protein transcription factor (ZFP TF™), designed to upregulate the expression of the gene encoding vascular endothelial growth factor (VEGF-A) in spinal cord injury (SCI) models.
In addition to its effects on angiogenesis or blood vessel growth, VEGF-A has been demonstrated to have direct neurotrophic and neuroprotective properties in several models that assess nerve integrity and health.
In addition, Sangamo is currently developing SB-509, a plasmid formulation of this same ZFP TF, for the treatment of diabetic neuropathy and has two ongoing Phase 2 trials in this area.
Dr. Fehlings and his colleagues observed that administration of the ZFP TF into the spinal cord at the time of injury produced measurable VEGF ZFP TF and increased levels of all of the major isoforms of the VEGF protein. They observed a corresponding neuroprotective effect with a statistically significant decrease in nerve fiber degradation and post-injury nerve cell death. They also noted an increase in blood vessel density around the injury.
Most importantly, in a severe model of SCI where animals are paraplegic post- injury, they observed a statistically significant (p<0.0001) improvement of hind-limb function over time.
"I am very impressed by the improvements that we were able to generate through treatment of acutely injured spinal cord with the VEGF ZFP TF," stated Dr. Fehlings.
"In earlier studies we had observed clear increases in VEGF protein levels and good evidence of a neuroprotective effect of the ZFP TF. In these more recent experiments we have seen evidence of improved functional outcomes that are quite impressive compared with any other therapeutic approach that we have evaluated including stem cell therapies,” he continued.
“We look forward to continuing these studies in collaboration with Sangamo and believe that this VEGF-activating ZFP TF may hold promise as a unique therapy for spinal cord injury and other forms of neural injury."