fULM-RTX: Functional ultrasound localization microscopy for monitoring RTX-001 efficacy and biomarker discovery

Vascular instability driven by early pericyte dysfunction and inflammation is increasingly recognized as a root cause of cardiovascular, renal, ocular, and neurodegenerative diseases. Despite their high prevalence, no curative therapies exist. Hereditary Hemorrhagic Telangiectasia (HHT)—a rare, genetically defined vascular disorder affecting approximately 1.4 million people worldwide—offers an ideal model to study these mechanisms. Patients with HHT suffer from recurrent nosebleeds, gastrointestinal bleeding, anemia, and arteriovenous malformations in vital organs, often leading to stroke, abscesses, heart failure, and neurological damage. The disease imposes a significant clinical and economic burden, exceeding €40,000 per patient annually, with no approved treatments available.

RougeTx aims to restore vascular stability and integrity in HHT through small-molecule therapeutics. Building on discoveries from Leiden University Medical Center (LUMC)—where thalidomide was shown to reduce bleeding by targeting pericytes—RougeTx developed RTX-001, an optimized pomalidomide analog suitable for chronic use. RTX-001 (currently at TRL 4) restores pericyte–endothelial interactions, prevents vascular malformations in HHT models, and demonstrates favorable safety and pharmacokinetics.

The project introduces an innovative collaboration between RougeTx and LUMC to integrate advanced imaging and molecular profiling technologies. Using functional Ultrasound Localization Microscopy (fULM), recently developed at LUMC, the team will non-invasively monitor vascular function and combine this with single-cell RNA sequencing (scRNA-seq) to map RTX-001’s effects on pericyte gene expression and vessel integrity.

Deliverables include validated quantitative biomarkers, a mechanistic understanding of RTX-001’s action, and a translational framework linking preclinical and clinical datasets. Together, these efforts will accelerate the development of a first-in-class therapy for HHT and open new therapeutic pathways for widespread vascular diseases associated with pericyte dysfunction.