Novel therapeutic target discovery platform for neurodegenerative diseases using VEGF and single-cell sequencing

Overview

This research initiative addresses a critical unmet need in neurodegenerative disease treatment by investigating VEGF (vascular endothelial growth factor) dysregulation as a central pathological mechanism. The platform targets major neurodegenerative conditions including Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease, Parkinson's disease, Multiple Sclerosis (MS), Huntington's disease, and diabetic neuropathy, all of which involve progressive neuronal degeneration with poorly understood underlying mechanisms.

The approach combines proprietary tissue-specific and inducible VEGF transgenic mouse models with advanced single-cell sequencing technology to map disease pathways at cellular resolution. By dynamically modulating VEGF expression in specific cell types and correlating these changes with phenotypic outcomes, the platform aims to identify critical cell populations and target genes involved in disease progression. This integrated methodology offers pharmaceutical and biotechnology partners a powerful discovery engine for novel neuroprotective therapeutics.

Technical specifications

Proprietary VEGF transgenic mouse models:

• Exclusive capability to generate tissue-specific and inducible VEGF knockout models, a capability currently limited globally
• Three distinct expression models in development: vascular endothelial cell-specific, macrophage-specific, and neuron-specific VEGF modulation
• CRISPR-dCas9-mediated gene editing combined with tetracycline-regulated inducible and reversible gene expression for real-time VEGF modulation

Single-cell sequencing and computational analysis:

• Single-cell RNA sequencing (scRNA-seq) for high-resolution cellular profiling
• Multi-omics analysis of human and mouse brain tissue samples
• Computational construction of cellular interaction networks for VEGF signaling pathways
• Integration of mouse model phenotypic data with network analysis to pinpoint pathological targets

Scientific rationale:

• VEGF-A functions as a neurotrophic factor supporting neuron survival and neurogenesis in both normal and pathological central nervous system conditions
• The growth factor demonstrates neuroprotective effects across multiple neurodegenerative disease models
• Cell-type-specific analysis reveals previously unrecognized VEGF signaling mechanisms

Technology readiness level

The platform builds on validated foundational work, including established tissue-specific VEGF mouse model generation and ongoing collaboration with single-cell sequencing expertise. Current development focuses on creating three new inducible VEGF expression models using advanced gene-editing techniques. The research program is positioned to advance from model creation through phenotypic characterization to target identification, with future validation involving computational analysis of human and mouse brain single-cell multi-omics data to identify disease-relevant cell types and therapeutic target genes.