Nanobodies: new avenue to treat kidney disease

Wanner, Nicola; Eden, Thomas Watts; Liaukouskaya, Nastassia; Koch‐Nolte, Friedrich

doi:10.1007/s00441-021-03479-8

Cited by 9 publications

(10 citation statements)

References 119 publications

(124 reference statements)

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“…Nanobodies that recognize P2X7 can effectively block the release of IL‐1β induced by ATP and have sub‐nanomolar affinity. In addition, the ability of Nanobody Dano1 generated for human P2X7 to inhibit IL‐1β emission is 1000 times greater than that of the small molecule drugs currently developed for P2X7 295 …”

Section: Nanobodies Controlling Csmentioning

confidence: 99%

“…In addition, the ability of Nanobody Dano1 generated for human P2X7 to inhibit IL-1β emission is 1000 times greater than that of the small molecule drugs currently developed for P2X7. 295 Expression levels of CXCL10 are elevated following infection with SARS-CoV-2. There are several nanobodies that target chemokine receptors that have been described, including CXCR4 and ChemR23.…”

Section: Cytokines Cleaned Away By Nanobodiesmentioning

confidence: 99%

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COVID‐19 cooling: Nanostrategies targeting cytokine storm for controlling severe and critical symptoms

Zheng,

Li,

et al. 2023

Medicinal Research Reviews

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As severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants continue to wreak havoc worldwide, the “Cytokine Storm” (CS, also known as the inflammatory storm) or Cytokine Release Syndrome has reemerged in the public consciousness. CS is a significant contributor to the deterioration of infected individuals. Therefore, CS control is of great significance for the treatment of critically ill patients and the reduction of mortality rates. With the occurrence of variants, concerns regarding the efficacy of vaccines and antiviral drugs with a broad spectrum have grown. We should make an effort to modernize treatment strategies to address the challenges posed by mutations. Thus, in addition to the requirement for additional clinical data to monitor the long‐term effects of vaccines and broad‐spectrum antiviral drugs, we can use CS as an entry point and therapeutic target to alleviate the severity of the disease in patients. To effectively combat the mutation, new technologies for neutralizing or controlling CS must be developed. In recent years, nanotechnology has been widely applied in the biomedical field, opening up a plethora of opportunities for CS. Here, we put forward the view of cytokine storm as a therapeutic target can be used to treat critically ill patients by expounding the relationship between coronavirus disease 2019 (COVID‐19) and CS and the mechanisms associated with CS. We pay special attention to the representative strategies of nanomaterials in current neutral and CS research, as well as their potential chemical design and principles. We hope that the nanostrategies described in this review provide attractive treatment options for severe and critical COVID‐19 caused by CS.

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Section: Nanobodies Controlling Csmentioning

confidence: 99%

Section: Cytokines Cleaned Away By Nanobodiesmentioning

confidence: 99%

COVID‐19 cooling: Nanostrategies targeting cytokine storm for controlling severe and critical symptoms

Zheng,

Li,

et al. 2023

Medicinal Research Reviews

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“…Biologics such as monoclonal antibodies and nanobodies that act on single target are advancing kidney diseases with improvements in bioavailability and tissue targeting. 69,70 Likewise, RNA-based short interfering RNAs and long coding RNAs are advancing to treat kidney diseases.…”

Section: Other Potential Multi-target Drugs For Kidney Diseasesmentioning

confidence: 99%

“…Developing biologics and RNA-based drugs with multi-target activities for kidney and glomerular diseases could have kidney and cell targeting advantages; however, several challenges remain that would need to be overcome. 69,70,71,72 Consequently, there is ample avenues to be investigated in developing multi-target therapies for kidney diseases.…”

Section: Other Potential Multi-target Drugs For Kidney Diseasesmentioning

confidence: 99%

“…An alternative strategy for limiting unwanted side effects of small molecules is to develop multi-target biologics and RNA-based therapies for kidney diseases. Biologics such as mAbs and nanobodies, which act on a single target, are advancing the treatment of kidney diseases with improvements in bioavailability and tissue targeting (68,69). Likewise, RNA-based short-interfering RNAs and long-coding RNAs are improving the treatment of kidney diseases.…”

Section: Other Potential Multi-target Drugs For Kidney Diseasesmentioning

confidence: 99%

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Multi-Target Drugs for Kidney Diseases

2021

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Kidney diseases such as acute kidney injury (AKI), chronic kidney disease (CKD), and glomerular nephritis can lead to dialysis and the need for kidney transplantation. The pathologies for kidney diseases are extremely complex, progress at different rates, and involve several cell types and cell-signaling pathways. Complex kidney diseases require therapeutics that can act on multiple targets. In the past ten years, in silico design of drugs has allowed for multi-target drugs to go quickly from concept to reality. Several multi-target drugs have been successfully made that target arachidonic acid pathways and transcription factors to treat inflammatory, fibrotic, and metabolic diseases. Multi-target drugs have also demonstrated great potential to treat diabetic nephropathy and fibrotic kidney disease. These drugs act by decreasing renal transforming growth factor-β (TGF-β) signaling, inflammation, mitochondrial dysfunction, and oxidative stress. There are several other recently developed multi-target drugs that have yet to be tested for their ability to combat kidney diseases. Overall, there is excellent potential for multi-target drugs that act on several cell types and signaling pathways to treat kidney diseases.

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Filtration and tubular handling of EWE‐hC3Nb1, a complement inhibitor nanobody, in wild type mice and a mouse model of proteinuric kidney disease

Fast,

Weyer,

Pedersen

et al. 2024

FEBS Open Bio

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Tubular activation and deposition of filtered complement proteins have been implicated in the progression of proteinuric kidney disease. The potent C3b‐specific nanobody inhibitor of the alternative pathway, EWE‐hC3Nb1, is likely freely filtered in the glomerulus to allow complement inhibition in the tubular lumen and may provide a novel treatment option to prevent tubulointerstitial injury. However, more information on the pharmacokinetic properties and renal tubular handling of EWE‐hC3Nb1 nanobody is required for its pharmacological application in relation to kidney disease. Here, we examined the pharmacokinetic properties of free EWE‐hC3Nb1 in mouse plasma and urine, following subcutaneous injection in wild‐type control and podocin knock out (KO) mice with severe proteinuria. Tubular handling of filtered EWE‐hC3Nb1 was assessed by immunohistochemistry (IHC) on kidney tissue from control, proteinuric mice, and KO mice deficient in the proximal tubule endocytic receptor megalin. Rapid plasma absorption and elimination of EWE‐hC3Nb1 was observed in both control and proteinuric mice; however, urinary excretion of EWE‐hC3Nb1 was markedly increased in proteinuric mice. Urinary EWE‐hC3Nb1 excretion was amplified in megalin KO mice, and substantial accumulation of EWE‐hC3Nb1 was observed in megalin‐expressing renal proximal tubules by IHC. Moreover, free EWE‐hC3Nb1 was found to be rapidly cleared from plasma. In conclusion, filtered EWE‐hC3Nb1 is reabsorbed by a megalin‐dependent process in the proximal tubules. Increased load of filtered proteins in the tubular fluid may inhibit the megalin‐dependent uptake of EWE‐hC3Nb1 in proteinuric mice. Treatment with EWE‐hC3Nb1 may allow investigation of the effects of complement inhibition in the tubular fluid.

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Nanobodies: new avenue to treat kidney disease

Cited by 9 publications

References 119 publications

COVID‐19 cooling: Nanostrategies targeting cytokine storm for controlling severe and critical symptoms

COVID‐19 cooling: Nanostrategies targeting cytokine storm for controlling severe and critical symptoms

Multi-Target Drugs for Kidney Diseases

Filtration and tubular handling of EWE‐hC3Nb1, a complement inhibitor nanobody, in wild type mice and a mouse model of proteinuric kidney disease

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