Modeling Pkd1 gene-targeted strategies for correction of polycystic kidney disease

Kurbegovic, Almira; Pacis, Rey Christian; Trudel, Marie

doi:10.1016/j.omtm.2023.03.016

Cited by 3 publications

(1 citation statement)

References 53 publications

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“…Arginine has many functions in human physiology and pathology. Many disorders mediated by arginine and its metabolites have been intensively studied recently [ 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. The equilibrium of arginine production in the human body by physiological adaption or by pharmacological therapies could be an efficient method for the prevention or treatment of L-arginine–NO pathway metabolic alteration-associated diseases [ 63 , 64 , 65 , 66 , 67 , 68 , 69 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of the L-Arginine–Nitric Oxide Molecular Pathway in Autosomal Dominant Polycystic Kidney Disease

Ene,

Penescu,

Nicolae

et al. 2024

JPM

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Recently, arginine has been proven to play an important role in ADPKD physiopathology. Arginine auxotrophy in ADPKD induces cell hyperproliferation, blocking the normal differentiation of renal tube cells and causing cyst formation. We explored the L-arginine (Arg)–nitric oxide (NO) molecular pathway in ADPKD, a multisystemic arginine auxotrophe disease. We developed a prospective case–control study that included a group of 62 ADPKD subjects with an estimated filtration rate over 60 mL/min/1.73 mp, 26 subjects with chronic kidney disease with an eGFR > 60 mL/min/1.73 mp, and a group of 37 healthy subjects. The laboratory determinations were the serum level of arginine, the enzymatic activity of arginase 2 and inducible nitric oxide synthase, the serum levels of the stable metabolites of nitric oxide (nitrate, direct nitrite, and total nitrite), and the endogenous inhibitors of nitric oxide synthesis (asymmetric dimethylarginine and symmetric dimethylarginine). In the ADPKD group, the levels of the arginine and nitric oxide metabolites were low, while the levels of the metabolization enzymes were higher compared to the control group. Statistical analysis of the correlations showed a positive association between the serum levels of Arg and the eGFR and a negative association between Arg and albuminuria. ADPKD is a metabolic kidney disease that is auxotrophic for arginine. Exploring arginine reprogramming and L-Arg–NO pathways could be an important element in the understanding of the pathogenesis and progression of ADPKD.

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Section: Discussionmentioning

confidence: 99%

The Role of the L-Arginine–Nitric Oxide Molecular Pathway in Autosomal Dominant Polycystic Kidney Disease

Ene,

Penescu,

Nicolae

et al. 2024

JPM

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Genetics of Chronic Kidney Disease

Vivante

2024

N Engl J Med

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Prospects for gene therapy in polycystic kidney disease

Chakraborty,

2024

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review We aim to provide an updated perspective on the recent advancements in gene therapy for polycystic kidney disease (PKD), a genetic disorder with significant morbidity. Given the rapid evolution of gene therapy technologies and their potential for treating inherited diseases, this review explores the therapeutic prospects and challenges in applying these technologies to PKD. Recent findings Significant progress has been made in understanding the genetic underpinnings of PKD, making it a prime candidate for gene therapy. Re-expression of the PKD genes, treatment with the C-terminal tail of polycystin 1 protein and antagomir therapy against miR-17 have shown promise in reducing cyst formation and preserving kidney function. The rapid development of gene-editing tools, antisense oligonucleotide-based strategies, programmable RNA, and advanced gene delivery systems has opened new possibilities for PKD treatment. However, challenges such as off-target effects, delivery efficiency, and long-term safety remain significant barriers to clinical application. Summary Current research highlights the transformative potential of gene therapy for PKD. Ongoing studies are crucial to overcoming existing challenges and translating these findings into clinical practice. We highlight the need for multidisciplinary efforts to optimize gene-editing technologies and ensure their safety and efficacy in treating PKD.

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Modeling Pkd1 gene-targeted strategies for correction of polycystic kidney disease

Cited by 3 publications

References 53 publications

The Role of the L-Arginine–Nitric Oxide Molecular Pathway in Autosomal Dominant Polycystic Kidney Disease

The Role of the L-Arginine–Nitric Oxide Molecular Pathway in Autosomal Dominant Polycystic Kidney Disease

Genetics of Chronic Kidney Disease

Prospects for gene therapy in polycystic kidney disease

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