2026-06-16 カリフォルニア大学ロサンゼルス校（UCLA）
＜関連情報＞
- https://newsroom.ucla.edu/releases/ucla-researchers-damaged-kidneys-drug
- https://www.cell.com/cell-stem-cell/abstract/S1934-5909(26)00203-1
ヒト化モノクローナル抗体によるENPP1阻害は、急性腎障害後の腎修復を促進する ENPP1 blockade with a humanized monoclonal antibody enhances renal repair after acute kidney injury
Lianjiu Su ∙ Qihao Sun ∙ Ziheng Zhou ∙ … ∙ Thomas Graeber, ∙ Shen Li ∙ Arjun Deb
Cell Stem Cell Published:June 16, 2026
DOI:https://doi.org/10.1016/j.stem.2026.05.011
Graphical abstract
Highlights
- Genetic deletion of ENPP1 promotes renal repair in pre-clinical injury models
- Humanized anti-ENPP1 antibody enhances renal repair and tubular proliferation
- The humanized antibody is well tolerated in non-human primates
Summary
The kidney possesses a poor ability to robustly regenerate and repair after acute injury. We show that the ectonucleotidase ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase-1) is robustly expressed in diseased human kidneys and strongly correlates with clinical indices of renal dysfunction. Genetic targeting of Enpp1 in mice enhanced renal repair. A humanized monoclonal antibody, targeting human ENPP1 (hENPP1mAb), when administered in humanized mice, led to tubular cell proliferation, enhanced renal glomerular filtration rate, decreased fibrosis, and rescued renal function after kidney injury. hENPP1mAb augmented nucleotide metabolism and cellular energetics, enabling proliferation and rescuing cell cycle arrest. Single-cell transcriptomics demonstrated expanded signatures of effective repair with hENPP1mAb. In a good laboratory practice (GLP)-compliant dose escalation study, hENPP1mAb was found to be non-toxic and highly tolerated in non-human primates. Our findings identify ENPP1 as a central regulator of acute kidney injury and demonstrate the therapeutic benefit of targeting ENPP1 ectonucleotidase activity with a humanized monoclonal antibody.
