PR-21

A cell mobility activator for the treatment of Acute Spinal Cord Injury

The types of disorders (motor, sensory, neurovegetative, genitosexual, etc.) observed following spinal cord injury not only indicate the poor capacity of neurons to regenerate their damaged or severed axons, but also the non-permissive environment that surrounds them.
To simultaneously influence these two parameters, Pharmaxon has developed a PSA-NCAM mimetic peptide that mimics PSA effects on cell mobility modulation. Using this compound, Pharmaxon intends to:

  • Stimulate the inherent regrowth capacity of axons,
  • Reduce glial scarring (astrocytes gradually form a physicochemical barrier – the glial scar – that inhibits axon regrowth),
  • Maximise the potential of regrowth-stimulating messages in a particularly inhibiting environment (NOGO proteins, proteins associated with myelin, proteoglycans, semaphorins, etc.)

PR-21 is currently evaluated in a preclinical toxicology study, with the final results expected in the fourth quarter of 2011. 
In the short term, the aim is to develop PR-21 as a monotherapy to regenerate spinal cord motor functions before lesions can definitively take root. In the mid term, Pharmaxon aims at assessing the drug’s efficacy as an adjuvant to stimulate the migration of neurons grafted to damaged areas.

Download a factsheet on PR-21 and its applications

Demonstrating proof-of-principle

The efficacy and safety of PR-21 have been demonstrated both in vitro and in vivo.

On cellular models

PR-21 mimics PSA effects on neuronal regrowth, migration of neuroblasts, fasciculation, and axon guidance. PR-21 also prevents the death of neurons by inhibiting glutamate releases (an excitatory neurotransmitter whose excessive synthesis provokes neuronal death).

PR-21 promotes migration of neuroblasts

On animals models of spinal cord injury

In a dorsal spinal cord hemi-section model, the single administration of PR-21 during the acute phase results in:

  • Major motor recovery,
  • Faster return to continence,
  • Significant reduction of post-traumatic glial scar size.

In order to reproduce the same clinical picture in humans, the efficacy of PR-21 was assessed in a spinal cord contusion model. Following a 14-day treatment, the results of this trial revealed significant motor recovery: 2 months after the initial injury, 80% of the rats with a damaged spinal cord regained the ability to walk in a coordinated manner.

PR-21 promotes motor recovery