Netrin-1 Mimetic Peptide Amphiphile Assemblies

NU 2024-174

INVENTORS

• Samuel Stupp*
• Cara Smith
• Zaida Alvarez Pinto

SHORT DESCRIPTION

Nanofiber-shaped supramolecular assemblies that mimic netrin-1 bioactivity to stimulate neurite growth and synaptic maturation for enhanced CNS regeneration.

BACKGROUND

Neurotrophic factors are essential for the development and regeneration of neurons; however, injuries in the central nervous system create inhibitory environments that limit natural recovery. Conventional therapeutic approaches with native netrin-1 are challenged by short half-lives and high dosage requirements, calling for innovative biomimetic solutions.

ABSTRACT

This invention details the development of a nanofiber-shaped supramolecular mimetic of netrin-1 where peptide amphiphiles incorporate a cyclic peptide sequence to activate the DCC receptor. Through a combination of imaging and computational analysis, the fibrous assembly has been shown to enhance neurite outgrowth, synaptic protein expression, and electrical activity in primary cortical neurons at low monomer ratios.

By addressing the limitations of native netrin-1 therapies, these supramolecular nanostructures offer a promising platform for treating CNS injuries. Their integration into hydrogel systems further broadens potential applications in regenerative therapies for spinal cord injuries, stroke, peripheral nerve injuries, and neurodegenerative diseases.

APPLICATIONS

• Spinal cord injury therapeutic
• Stroke therapeutic
• Neurodegenerative disease therapeutic such as Alzheimer’s disease.

ADVANTAGES

• Overcomes challenges associated with using native and recombinant netrin-1 proteins as therapies such as short half-lives and costly high dosage.
• Efficient receptor activation and effective neurite extension and synaptic maturation.
• Incorporation into supramolecular hydrogel systems to promote recovery following spinal cord injury.

PUBLICATIONS

• Samuel Stupp*, Cara Smith, Zaida Alvarez Pinto, Enhanced Neuron Growth and Electrical Activity by a Supramolecular Netrin-1 Mimetic Nanofiber ACS Nano October 4 2023

IP STATUS

US Patent Pending