During development of the nervous system, CSPGs guide the formation of neural connections. As the central nervous system matures, they settle into perineuronal nets, specialized structures that stabilize synaptic activity.
After injury, however, CSPG production surges. What once helped build the nervous system now prevents it from repairing itself.
After nervous system damage, the body mounts a defense. Reactive astrocytes form a glial scar, a dense molecular barrier around the damaged tissue.
The protective nature of the glial scar comes at a long-term cost, upregulating the production of CSPGs, an inhibitor of axonal growth.
The key to modulating CSPG inhibition lies in the neuronal receptor protein tyrosine phosphatase sigma (PTPσ). NVG-291 is a first-in-class peptide mimetic of the PTPσ wedge domain, designed to unlock the nervous system’s ability to reform neural connections and restore lost function.
The CSPG-PTPσ pathway is not unique to spinal cord injury. CSPG upregulation is conserved across a wide range of neurotraumatic injuries and neurologic conditions.
Wherever CSPGs accumulate, they block endogenous repair processes. This conserved mechanism allows for NVG-291’s approach to potentially extend well beyond a single condition as a pipeline in a product.
