Computational drug repositioning of clopidogrel as a novel therapeutic option for focal segmental glomerulosclerosis

Clopidogrel for Proteinuria Reduction in Focal Segmental Glomerulosclerosis: Phase 2 Trial Design

“…Including patients with genetic and primary FSGS is consistent with the original network-based analyses that identified clopidogrel to interfere with FSGS development and progression via several signaling cascades, mediated by its anticoagulant, anti-inflammatory, antioxidant, immunosuppressive, and proautophagic functions. 3 Interestingly, recent experimental and clinical data also suggest that the P2Y12 subtype of ADP receptor is a driver of renal fibrosis and the use of clopidogrel might slow the decline of estimated glomerular filtration rate in patients with chronic kidney disease. 5 The similarity of inclusion ( Supplementary Table S1 ) and exclusion criteria ( Supplementary Table S2 ) to the recent DUET trial will also allow comparison of the results of our study with this study, which includes a similar unselected population with primary FSGS.…”

“… 2 Recently, this approach has identified the antiplatelet drug clopidogrel as a novel repositioning candidate. 3 Clopidogrel is known to inhibit the P2Y12 subtype of ADP receptor, which is important in activation of platelets, but also demonstrates anticoagulant, anti-inflammatory, antioxidant, immunosuppressive, and proautophagic effects that could counterbalance dysregulated FSGS pathways ( Supplementary Figure S1 , Supplementary Methods ). Significant reduction of proteinuria and improved renal histomorphology in the adriamycin FSGS mouse model provided experimental validation of the in silico prediction and suggests that clopidogrel is a promising candidate for clinical testing in patients with FSGS.…”

“…Significant reduction of proteinuria and improved renal histomorphology in the adriamycin FSGS mouse model provided experimental validation of the in silico prediction and suggests that clopidogrel is a promising candidate for clinical testing in patients with FSGS. 3 …”

Focal Segmantal Glomerulosclerosis: Epidemiological, Clinico-Biological, Pathological, Etiological, Therapeutic and Evolutionary Profiles in Dakar

“…However 84.81% of patients with FSGS had normal sized kidneys which probably relates to tubulointerstitial infiltrates, edema, fibrosis and dilated tubules as seen in HIVAN cases [8] [14]- [18]. These data, along with a favorable drug safety profile, endorse clopidogrel as an attractive candidate for drug repositioning and subsequent clinical trial evaluation for patients suffering from FSGS [20] [21] [22].…”