Targeting and therapeutic peptide-based strategies for polycystic kidney disease

Wang, Jonathan; Tripathy, Nirmalya; Chung, Eun Ji

doi:10.1016/j.addr.2020.08.011

Cited by 12 publications

(4 citation statements)

References 178 publications

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“…Related to the knowledge gap present in genetic kidney disease etiology, another challenge that still remains in renal drug delivery is that, in general, ligands that are available for targeting specific kidney cell types are limited and few. For instance, although a handful of peptides that target the proximal tubule, distal tubule, cortical collecting duct, glomerulus, and podocytes have been identified, their validation within a disease indication is limited. ,, Thus, methods such as in vivo phage display, aptamer discovery, and molecular dynamics and in silico approaches that can establish ligands and demonstrate specificity and high affinity to specific renal cell types or even immune cells that participate in the disease are needed. By doing so, these ligands can be conjugated to drugs or decorated onto nanoparticles to be tailored for diseases where specific cell types are of particular concern.…”

Section: Challenges and A Call To Actionmentioning

confidence: 99%

Spotlight on Genetic Kidney Diseases: A Call for Drug Delivery and Nanomedicine Solutions

et al. 2023

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Nanoparticles as drug delivery carriers have benefited diseases, including cancer, since the 1990s, and more recently, their promise to quickly and efficiently be mobilized to fight against global diseases such as in the COVID-19 pandemic have been proven. Despite these success stories, there are limited nanomedicine efforts for chronic kidney diseases (CKDs), which affect 844 million people worldwide and can be linked to a variety of genetic kidney diseases. In this Perspective, we provide a brief overview of the clinical status of genetic kidney diseases, background on kidney physiology and a summary of nanoparticle design that enable kidney access and targeting, and emerging technological strategies that can be applied for genetic kidney diseases, including rare and congenital kidney diseases. Finally, we conclude by discussing gaps in knowledge remaining in both genetic kidney diseases and kidney nanomedicine and collective efforts that are needed to bring together stakeholders from diverse expertise and industries to enable the development of the most relevant drug delivery strategies that can make an impact in the clinic.

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Section: Challenges and A Call To Actionmentioning

confidence: 99%

Spotlight on Genetic Kidney Diseases: A Call for Drug Delivery and Nanomedicine Solutions

et al. 2023

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“…The ABCB5 + MSCs have been studied in polycystic kidney disease (PKD), a group of inherited nephropathies characterized by the formation of multiple fluid-filled cysts in the kidney, which distorts the renal architecture and severely impairs filtration function [129,130]. In the PKD/Mhm (Cy/+) rat model of the most common PKD type, i.e., autosomal dominant PKD (ADPKD) [131], systemic infusions of ABCB5 + MSCs elicited in the kidney cells a reversion of metabolic reprogramming from ADPKD-typical upregulation of alternative pathways of energy production such as glycolysis to oxidative phosphorylation, citrate cycle, gluconeogenesis, and pyruvate metabolism pathways [132].…”

Section: Effects On Parenchymal Cellsmentioning

confidence: 99%

Skin-Derived ABCB5+ Mesenchymal Stem Cells for High-Medical-Need Inflammatory Diseases: From Discovery to Entering Clinical Routine

Niebergall-Roth¹,

Frank

Ganss

et al. 2022

IJMS

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The ATP-binding cassette superfamily member ABCB5 identifies a subset of skin-resident mesenchymal stem cells (MSCs) that exhibit potent immunomodulatory and wound healing-promoting capacities along with superior homing ability. The ABCB5+ MSCs can be easily accessed from discarded skin samples, expanded, and delivered as a highly homogenous medicinal product with standardized potency. A range of preclinical studies has suggested therapeutic efficacy of ABCB5+ MSCs in a variety of currently uncurable skin and non-skin inflammatory diseases, which has been substantiated thus far by distinct clinical trials in chronic skin wounds or recessive dystrophic epidermolysis bullosa. Therefore, skin-derived ABCB5+ MSCs have the potential to provide a breakthrough at the forefront of MSC-based therapies striving to fulfill current unmet medical needs. The most recent milestones in this regard are the approval of a phase III pivotal trial of ABCB5+ MSCs for treatment of recessive dystrophic and junctional epidermolysis bullosa by the US Food and Drug Administration, and national market access of ABCB5+ MSCs (AMESANAR®) for therapy-refractory chronic venous ulcers under the national hospital exemption pathway in Germany.

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“…At present, there is only tolvaptan, a vasopressin type 2 receptor antagonist that is approved as a therapeutic medication for ADPKD [12][13][14]. However, the patients with long-term use of tolvaptan will face a high risk of liver injury [15][16][17][18][19]. Therefore, there is still an urgent need to discover therapeutic drugs that are effective against ADPKD with fewer adverse effects.…”

Section: Introductionmentioning

confidence: 99%

1-Indanone retards cyst development in ADPKD mouse model by stabilizing tubulin and down-regulating anterograde transport of cilia

Ran

Zhou

et al. 2022

Acta Pharmacol Sin

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Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. Cyst development in ADPKD involves abnormal epithelial cell proliferation, which is affected by the primary cilia-mediated signal transduction in the epithelial cells. Thus, primary cilium has been considered as a therapeutic target for ADPKD. Since ADPKD exhibits many pathological features similar to solid tumors, we investigated whether targeting primary cilia using anti-tumor agents could alleviate the development of ADPKD. Twenty-four natural compounds with anti-tumor activity were screened in MDCK cyst model, and 1-Indanone displayed notable inhibition on renal cyst growth without cytotoxicity. This compound also inhibited cyst development in embryonic kidney cyst model. In neonatal kidney-specific Pkd1 knockout mice, 1-Indanone remarkably slowed down kidney enlargement and cyst expansion. Furthermore, we demonstrated that 1-Indanone inhibited the abnormal elongation of cystic epithelial cilia by promoting tubulin polymerization and significantly down-regulating expression of anterograde transport motor protein KIF3A and IFT88. Moreover, we found that 1-Indanone significantly down-regulated ciliary coordinated Wnt/β-catenin, Hedgehog signaling pathways. These results demonstrate that 1-Indanone inhibits cystic cell proliferation by reducing abnormally prolonged cilia length in cystic epithelial cells, suggesting that 1-Indanone may hold therapeutic potential to retard cyst development in ADPKD.

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Targeting and therapeutic peptide-based strategies for polycystic kidney disease

Cited by 12 publications

References 178 publications

Spotlight on Genetic Kidney Diseases: A Call for Drug Delivery and Nanomedicine Solutions

Spotlight on Genetic Kidney Diseases: A Call for Drug Delivery and Nanomedicine Solutions

Skin-Derived ABCB5+ Mesenchymal Stem Cells for High-Medical-Need Inflammatory Diseases: From Discovery to Entering Clinical Routine

1-Indanone retards cyst development in ADPKD mouse model by stabilizing tubulin and down-regulating anterograde transport of cilia

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