BDNF Mimetic Peptide Amphiphiles

BDNF Mimetic Peptide Amphiphile for Enhanced Neurotrophic Signaling and Neuronal Regeneration

NU 2018-020

INVENTORS

• Samuel Stupp
• Alexandra Kolberg
• Zaida Alvarez Pinto

SHORT DESCRIPTION

This technology is an injectable, highly potent peptide amphiphile that mimics BDNF function via the TrkB pathway while providing extracellular support. It promotes neuronal growth and signaling for regenerative treatments in CNS injuries and diseases.

BACKGROUND

Current treatments of central nervous system (CNS) struggle with unstable neurotrophic factors and inefficient brain delivery. In particular, native Brain-derived neurotrophic factor (BDNF) protein-based therapies have had little clinical success due to their suboptimal pharmacological properties.

ABSTRACT

The invention uses a novel peptide amphiphile (PA) with a cyclic peptide, which mimics BDNF function. The PA forms fibrous scaffold reminiscent of the extracellular matrix of the CNS. Notably, this BDNF mimetic peptide was found to be active only when displayed on a PA supramolecular nanostructure. When added to primary neurons in vitro, this PA activates the TrkB receptor after 4 hours of exposure. The BDNF-mimetic PA promotes the survival and neuronal outgrowth in vitro, as well as hind limb recovery in vivo mice model of spinal cord injury in an injectable formulation. 

APPLICATIONS

• Treatment of neurodegenerative diseases: e.g., Parkinson’s and Alzheimer’s diseases.
• Treatment of CNS injuries: e.g., spinal cord injuries.

ADVANTAGES

• Improves in vivo potency: Enhances neuropeptide stability and half-life.
• Enhances neuronal maturation: Increases electrical activity and signaling.
• Promotes axonal regeneration: Encourages neuron infiltration and axonal growth.

IP STATUS                                                                                                                                                                                                                           

Issued US Patent 12,122,811.

Confocal images of neuronal cells treated with BDNF peptide, E2 PA, BDNF PA, and BDNF protein for 24 h in vitro