Description:
Summary:
The National Eye Institute (NEI) seeks research co-development partners and/or licensees for the development of an eyedrop formulation to deliver a series of peptides as a gene-agnostic approach to treating inherited retinal diseases.
Description of Technology:
Retinitis pigmentosa (RP) is one of the most common inherited retinal diseases (IRDs) that is estimated to affect 1 in 4,000 people in the United States and worldwide. Over 100,000 people in the US, and 1.5 million people worldwide suffer from RP. RP leads to progressive photoreceptor cell degeneration and ultimately vision loss, with more than 90 genes implicated in molecular pathways towards photoreceptor cell death. Due to this high heterogeneity, therapeutic approaches targeting specific genes generally benefit few patients, while for most forms of RP few or no medical options are available.
Peptide drug development has made great progress recently thanks to new production, modification, and analytical technologies. Solutions of chemically synthesized bioactive peptides have unique advantages over mixed formulations. They are free of inactive ingredients that cause secondary effects. Structural biology and recombinant biologics aid in peptide design to modify amino acids, enhancing target affinity, specificity, and regulating bioactivity, as well as improving the solubility and stability of peptide drugs. Peptides can diffuse better than biologics (proteins, antibodies) with better penetrability. Compared with biologics, therapeutic peptides have demonstrably less immunogenicity and lower production costs.
This technology optimizes synthetic peptides that are soluble, stable, and protect the retina. A series of peptides derived from the neurotrophic region of PEDF 17-mer (human sequence 98-114 amino acids, N- and C-terminus uncapped) is designed and synthesized. They have a series of truncations from the amino and carboxy ends, and internal region, as well as isosteric amino acid replacements, and amino terminal additions such as capping (X) and amidation (Y) to prevent exopeptidases from degrading the peptide. The peptides are optimized to protect photoreceptors and other retinal cells against death and degeneration. They optimized for solubility, stability, efficacy, in protecting the retina at the structural, morphological and functional level. The peptides can be tested in vitro, ex vivo, in cells and in vivo using models of retinal degeneration. The peptides can be used as eyedrops in vivo.
Potential Commercial Applications:
- Potential simple and effective treatment for inherited eye diseases contributing to Retinitis Pigmentosa (RP) and macular degenerations, such as AMD and geographic atrophy
- Prevent disease progression by protecting degenerating photoreceptors
Competitive Advantages:
- Chemically synthesized bioactive peptide solutions are free of inactive ingredients that cause secondary effects as compared to mixed formulations
- Enhanced target affinity, specificity, bioactivity, as well as in improved solubility, and stability
- Peptides can diffuse better than biologics (proteins, antibodies) with better penetrability
- Compared to biologics, therapeutic peptides have demonstrably less immunogenicity and lower production costs
- Eye drop formulation is accessible to more patients and provides an easy administration route
- PEDF formulation mimics the natural protective process lost in patients with inherited eye diseases, contributing to RP