Using a Human Decedent Model to Elucidate the Mechanism of Action of Rilparencel, an Investigative Autologous Renal Cell Therapy for the Treatment of Chronic Kidney Disease (CKD)
Authors: Francesca Zanoni1,2, Joseph Stavas3, Michael Czerwinski3, Andrew Bruce3, Bruce Culleton3, Brendan Keating1,2, Robert Montgomery1,2, Anthony Conway3
1NYU Langone Transplant Institute, NYU Langone Health
2Department of Surgery, NYU Grossman School of Medicine
3ProKidney, LLC
Background: CKD is a global health burden with many patients progressing to end-stage kidney disease (ESKD). Rilparencel, an investigational autologous renal cell therapy, has shown promise in stabilizing kidney function in patients with advanced CKD in Phase 2 studies. A Phase 3 trial called REGEN-006 (NCT05099770) is underway. However, the molecular and cellular mechanisms of rilparencel are not well understood. An anticipated Research on Decedents Oversight Committee approval will govern the human decedent model to be used at NYU to investigate cellular and molecular changes and deep kidney functional assessment following kidney autotransplantation and may offer insights into the Mechanism of Action (MoA) of rilparencel.
Methods: The ProKidney-NYU Study will use this decedent model to investigate rilparencel’s MoA. Eligible brain-dead donors (>18 years, eGFR 20-60 mL/min/1.73m²) will undergo bilateral nephrectomies with external autotransplantation into the pelvis for easy accessibility. The right kidney will be biopsied for rilparencel manufacture (Day 0) followed by cell injection into the same kidney cortex on Day 22 (Fig. 1). Serial bilateral kidney biopsies with paired urine, serum, and blood samples will be collected over 61 days. Multi-omic analyses (spatial transcriptomics, snRNA/ATAC-Seq, spatial proteomics, spatial metabolomics) will be performed from both treated (right) and control (left) kidneys.
Results: Anticipated results include comparative analyses of multi-omic gene expression, protein abundance and metabolite profiles pre- & post-treatment. Single-cell and spatial datasets will be integrated with histopathological changes. The association of molecular findings with functional clinical outcomes will be assessed throughout the study.
Conclusions: Detailed characterization of rilparencel’s MoA using advanced multi-omic analyses in a decedent model could significantly enhance our understanding of autologous renal cell therapies in CKD treatment.
