Menlo Park, Calif.-based Geron Corporation (GERN) on January 17 said new studies show the company’s human embryonic stem cell (hESC)-based oligodendroglial progenitor therapeutic produces multiple nerve growth factors, proteins that stimulate the survival and regeneration of neurons damaged during spinal cord injury.
According to the company, the studies conducted by Geron scientists describe a newly discovered neurotrophic effect of a GRNOPC1 that, in addition to the previously documented in vivo remyelinating activity of these cells, serves as a second mechanism of action that demonstrates the product’s beneficial effects when injected into animal models of acute spinal cord injury.
The new studies were published in Stem Cells and Development (Vol. 15, Issue 6, 943-952).
“The work extends our knowledge of the multiple biological activities of GRNOPC1,” said CEO Thomas B. Okarma, M.D. “In addition to the remyelinating activity as previously reported, GRNOPC1 produces growth factors that can improve the survival and extension of neuronal circuitry in the spinal cord. The multiple functions of GRNOPC1 affirm the potential therapeutic utility of our cell-based approach to the repair of spinal cord injury and provide multiple mechanisms within a single therapy to achieve functional recovery.”
GRNOPC1 was found to produce numerous neurotrophic factors, including transforming growth factor (beta)1 (TGF-(beta)1), transforming growth factor (beta)2 (TGF-(beta)2), activin A, midkine, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF).
These factors were all produced at physiologically active levels, and each has been reported to have trophic effects on neurons associated with the spinal cord.
In spinal cord injury, neuronal cell loss can occur not only as a result of the physical trauma of the injury itself, but also due to the oxidative and inflammatory reaction that subsequently occurs.
The introduction of neurotrophic factors into the lesion site could increase neuronal survival, decrease dieback of neuronal axons and induce sprouting of new axons to allow formation of alternative circuitry.
The studies also demonstrate that neurotrophic factors produced by GRNOPC1 are biologically active.
When culture medium used to grow GRNOPC1 was applied to adult rat sensory neurons, sprouts called “neurites” emerged from the rat neurons.
Media that had not been exposed to GRNOPC1 stimulated significantly less neurite outgrowth.
“Our studies show that multiple neurotrophic factors are produced by GRNOPC1 that lead to neurite outgrowth,” said R. Scott Thies, Ph.D., Geron’s lead investigator on the work. “Depletion or inactivation of any single factor did not eliminate the neurotrophic activity exhibited by these cells.”
Geron is developing biopharmaceuticals for the treatment of cancer and degenerative diseases, including spinal cord injury, heart failure, diabetes and HIV/AIDS.
Contact: David L. Greenwood, 650-473-7765 info@geron.com
