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Cited by 44Genetic and Kidney Cyst DiseasesMicroRNA in disease regulationRNA Interference and Gene Delivery

Therapeutic microRNAs in polycystic kidney disease

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Yheskel, Matanel, Patel, Vishal·2017·Current Opinion in Nephrology and Hypertension
DOI 10.1097/mnh.0000000000000333PMC PMC6343829
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Abstract

PURPOSE OF REVIEW: microRNAs (miRNAs) are short noncoding RNAs that function as sequence-specific inhibitors of gene expression. Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetic cause of end-stage kidney failure with limited treatment options. The realization that miRNA upregulation, and thus its gain-of-function, can drive the progression of ADPKD has raised the possibility that anti-miRs represent a novel drug class for this disorder. RECENT FINDINGS: A common set of miRNAs are aberrantly expressed in various murine models of polycystic kidney disease. In particular two miRNAs, miR-17 family and miR-21, are both upregulated in kidney cysts and promote ADPKD progression in mouse models. miR-17 rewires cyst epithelial metabolism to enhance cyst proliferation. On the other hand, miR-21 represses proapoptotic genes and thus inhibits cyst apoptosis. Importantly, an anti-miR-17 drug has advanced through preclinical ADPKD studies, whereas an anti-miR-21 drug has already cleared phase I clinical trial. SUMMARY: miRNAs have emerged as new regulators of ADPKD pathogenesis. Anti-miRs represent a feasible and an entirely new class of drugs for the treatment of ADPKD.

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  • The anti-miR21 drug has cleared phase 1 clinical trial in polycystic kidney disease including Alport syndrome patients.

    “The anti-mir21 drug has already cleared phase 1 clinical trial in Polycystic kidney disease including Alport syndrome patients [101].”

    From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [101]

    The therapeutic-approach section says the anti-miR-21 drug RG-012 cleared a phase I trial and was then being tested in a phase II trial involving Alport syndrome patients. It does not say the phase I trial was in polycystic kidney disease or included Alport syndrome patients; it says whether the drug slows ADPKD progression remains to be seen. (LLM, conf=0.91)

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Cited by

Sorted by citations

Authors
Yheskel, M., & Patel, V.
Affiliations
The University of Texas Southwestern Medical Center (US)
Corresponding author
Patel, Vishal
ORCID
Venue
Current Opinion in Nephrology and Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2017-07
Volume
26
Issue
4
Pages
282-289
ISSN
1062-4821 (ISSN-L)
DOI
10.1097/mnh.0000000000000333
PMC
PMC6343829
OpenAlex
W2605223542
Cited by
44
References
2
Citations by year
2026: 2 · 2025: 7 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 1 · 2020: 10 · 2019: 6 · 2018: 6 · 2017: 3
FWCI
0.88
Type
journal article
Language
en
Open access
Locations
  • Current Opinion in Nephrology & Hypertension (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK102572)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
polycystic kidney disease, microRNA, anti-miR therapy, miR-17 family, miR-21, renal cysts, apoptosis, end-stage kidney failure, therapeutic target
MeSH terms
Animals, Disease Models, Animal, Gene Expression Regulation, Humans, Kidney Failure, Chronic, Oligonucleotides, Up-Regulation, Polycystic Kidney, Autosomal Dominant, Disease Progression, MicroRNAs, Mice

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