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Preclinical Studies of NRPs

Epilepsy - NRP2945:

  • Downregulates convulsive seizures after GABA A receptor system in-toxification (PTZ) by 90% and increases GABA A receptor subunit expression.
  • Provides neuroprotection in hippocampal / cortical areas after epileptic insult.
  • Maintains neuronal homeostasis (cell volume) during epileptogenesis.
  • Controls and decreases absence seizures (thalamus control) in genetic models of absence epilepsy (GAERs rats).
  • Initiates anti-epileptogenesis after states of Status Epilepticus (pilocarpine rats).
  • Increases memory consolidation and retrieval under generalized epileptic conditions (pilocarpine rats).

MotoR neurone Disease - NRP2945:

  • Provides muscle control as monotherapy or in adjunction with riluzole.
  • Progression-free survival period is extended in ALS mice.
  • 40-60% survival length increase.
  • Leads to downregulation of overstimulated CXCR4 cell surface receptors in cells of G93A gain-of-function mutant mice, thereby maintaining homeostasis.

Peripheral Neuropathy - NRP2945:

  • Mitigates toxicity and prevents death after mega-dosages of vitamin B6 intoxication in adult rats.
  • Preserves muscle control and agility in rats injected with high vitamin B6 dosages.
  • Has the potential be useful for virus-, diabetes-, chemotherapy-induced peripheral neuropathy conditions.

Multiple Sclerosis (MS) - NRP2945:

  • Has shown re-myelinating, axonal protection and neurite outgrowth promoting activity as well as anti-inflammatory activity in the central nervous system and periphery.
  • Increased clinically scored motor abilities to a high extent even when NRP2945 was administered at height of disease (MOG-EAE mice).
  • NRP2945 analogue with full patent life will be excellently suited for development of a highly efficacious therapy of progressive forms of MS.

Spinal Cord Injury (SCI) - NRP2945:

  • Provides for axonal regeneration during complete transection injury (hemisection SCI).
  • Inhibits astroglial and microglial formation within injury area.
  • Initiates neurogenesis and anti-inflammatory activity within in vitro models of trauma.

Glaucoma (ophthalmology) - NRP2945:

  • Is effective as an eye drop formulation in severe diseases concerning the back of the eye (optic nerve and receptor cell layer).
  • Provides neuroprotection and maintains physiological function in retina and optic nerve tissue.
  • Provides strong anti-inflammatory aspect in retina (downregulation of astrocytic proliferation during states of hypoxia).

In Summary

NRP2945 has consistently shown positive efficacy profiles in multiple rodent models of CNS injury / disease. NRPs are highly effective in the lower μg/kg range in rodents. We show strong effects in both prophylactic and therapeutic applications with peripheral NRP2945 administration. Peripheral subcutaneous injection is the preferred route of administration although other routes are being investigated.