Investigational agents for autosomal dominant polycystic kidney disease: preclinical and early phase study insights
Expert Opin Investig Drugs. 2024 Apr 15. doi: 10.1080/13543784.2024.2342327. Online ahead of print.ABSTRACTINTRODUCTION: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited kidney condition caused by a single gene mutation. It leads patients to kidney failure in more than 50% of cases by the age of 60, and, given the dominant inheritance, this disease is present in the family history in more than 90% of cases.AREAS COVERED: This review aims to analyze the set of preclinical and early phase studies to provide a general view of the current progress on ADPKD therapeutic options. Articles from Pub...
Source: Expert Opinion on Investigational Drugs - April 15, 2024 Category: Drugs & Pharmacology Authors: Irene Capelli Sarah Lerario Francesca Ciurli Gian Marco Berti Valeria Aiello Michele Provenzano Gaetano Manna Source Type: research
Long-term effectiveness and safety of tolvaptan in autosomal dominant polycystic kidney disease
CONCLUSIONS: This study shows a modest benefit of tolvaptan in ADPKD patients, as well as safety concerns.PMID:38616432 | DOI:10.1016/j.medcli.2024.01.026 (Source: Medicina Clinica)
Source: Medicina Clinica - April 15, 2024 Category: General Medicine Authors: Lorenzo Cantarelli Marta Guti érrez Valencia Leire Leache Alegria Luis Carlos Sainz Fernandez Juan Erviti Lopez Fernando Guti érrez Nicolas Gloria Julia Nazco Casariego Source Type: research
Investigational agents for autosomal dominant polycystic kidney disease: preclinical and early phase study insights
Expert Opin Investig Drugs. 2024 Apr 15. doi: 10.1080/13543784.2024.2342327. Online ahead of print.ABSTRACTINTRODUCTION: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited kidney condition caused by a single gene mutation. It leads patients to kidney failure in more than 50% of cases by the age of 60, and, given the dominant inheritance, this disease is present in the family history in more than 90% of cases.AREAS COVERED: This review aims to analyze the set of preclinical and early phase studies to provide a general view of the current progress on ADPKD therapeutic options. Articles from Pub...
Source: Expert Opinion on Investigational Drugs - April 15, 2024 Category: Drugs & Pharmacology Authors: Irene Capelli Sarah Lerario Francesca Ciurli Gian Marco Berti Valeria Aiello Michele Provenzano Gaetano Manna Source Type: research
Investigational agents for autosomal dominant polycystic kidney disease: preclinical and early phase study insights
Expert Opin Investig Drugs. 2024 Apr 21:1-16. doi: 10.1080/13543784.2024.2342327. Online ahead of print.ABSTRACTINTRODUCTION: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited kidney condition caused by a single-gene mutation. It leads patients to kidney failure in more than 50% of cases by the age of 60, and, given the dominant inheritance, this disease is present in the family history in more than 90% of cases.AREAS COVERED: This review aims to analyze the set of preclinical and early-phase studies to provide a general view of the current progress on ADPKD therapeutic options. Articles fro...
Source: Expert Opinion on Investigational Drugs - April 15, 2024 Category: Drugs & Pharmacology Authors: Irene Capelli Sarah Lerario Francesca Ciurli Gian Marco Berti Valeria Aiello Michele Provenzano Gaetano La Manna Source Type: research
Carnitine palmitoyltransferase II (CPT II) deficiency responsible for refractory cardiac arrhythmias, acute multiorgan failure and early fatal outcome
ConclusionsCPTII deficiency may be suspected in newborns showing cardiac arrhythmias, associated or not with hypertrophic cardiomyopathy, polycystic kidneys, brain malformations, hepatomegaly. Its diagnosis should be even more suspected and investigated in cases of increased plasmatic levels of creatine phosphokinase and acylcarnitines in addition to kidney, heart and liver dysfunctions, as occurred in the present patient. Accurate family history, extended metabolic screening, and multidisciplinary approach are necessary for diagnosis and adequate management of affected subjects. Next generation sequencing (NGS) techniques...
Source: Italian Journal of Pediatrics - April 14, 2024 Category: Pediatrics Source Type: research
Notch3 as a novel therapeutic target for the treatment of ADPKD by regulating cell proliferation and renal cyst development
Biochem Pharmacol. 2024 Apr 9:116200. doi: 10.1016/j.bcp.2024.116200. Online ahead of print.ABSTRACTAutosomal dominant polycystic kidney disease (ADPKD) is a common monogenic kidney disease. Emerging research indicates that the Notch signaling pathway plays an indispensable role in the pathogenesis of numerous kidney diseases, including ADPKD. Herein, we identified that Notch3 but not other Notch receptors was overexpressed in renal tissues from mice with ADPKD and ADPKD patients. Inhibiting Notch3 with γ-secretase inhibitors, which blocks a proteolytic cleavage required for Notch3 activation, or shRNA knockdown of Notch3...
Source: Biochemical Pharmacology - April 11, 2024 Category: Drugs & Pharmacology Authors: Limin Su Ting Chen Hongtao Hu Zifan Xu Xiande Luan Kequan Fu Ying Ren Dong Sun Ying Sun Dong Guo Source Type: research
Notch3 as a novel therapeutic target for the treatment of ADPKD by regulating cell proliferation and renal cyst development
Biochem Pharmacol. 2024 Apr 9:116200. doi: 10.1016/j.bcp.2024.116200. Online ahead of print.ABSTRACTAutosomal dominant polycystic kidney disease (ADPKD) is a common monogenic kidney disease. Emerging research indicates that the Notch signaling pathway plays an indispensable role in the pathogenesis of numerous kidney diseases, including ADPKD. Herein, we identified that Notch3 but not other Notch receptors was overexpressed in renal tissues from mice with ADPKD and ADPKD patients. Inhibiting Notch3 with γ-secretase inhibitors, which blocks a proteolytic cleavage required for Notch3 activation, or shRNA knockdown of Notch3...
Source: Biochemical Pharmacology - April 11, 2024 Category: Drugs & Pharmacology Authors: Limin Su Ting Chen Hongtao Hu Zifan Xu Xiande Luan Kequan Fu Ying Ren Dong Sun Ying Sun Dong Guo Source Type: research
Genes, Vol. 15, Pages 484: Exploring Adiponectin in Autosomal Dominant Kidney Disease: Insight and Implications
In conclusion, adiponectin levels and the presence of ADIPOQ rs1501299 genotype are significantly associated with a worse ADPKD phenotype, indicating that both could potentially provide important insights into the disease. Further studies are warranted to understand the pathophysiological role of adiponectin in ADPKD patients. (Source: Genes)
Source: Genes - April 11, 2024 Category: Genetics & Stem Cells Authors: Ersilia Nigro Marta Mallardo Maria Amicone Daniela D ’Arco Eleonora Riccio Maurizio Marra Fabrizio Pasanisi Antonio Pisani Aurora Daniele Tags: Article Source Type: research
The pathophysiology of polycystic liver disease
Polycystic liver disease (PLD) is a rare genetic disorder characterized by ≥10 cysts within the liver parenchyma. PLD occurs independently as autosomal dominant polycystic liver disease (ADPLD) or as extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). Although most patients with PLD are asymptomatic, a subset of patients will develop severe hepatomegaly affecting quality of life.1 (Source: Journal of Hepatology)
Source: Journal of Hepatology - April 9, 2024 Category: Gastroenterology Authors: Ren ée Duijzer, Melissa M. Boerrigter, Tom J.G. Gevers, Joost P.H. Drenth Tags: Hepatology Snapshot Source Type: research
Secondary infertility due to necrospermia in men with autosomal-dominant polycystic kidney disease: a report of two cases
We report two cases of secondary infertility in men with ADPKD. These men experienced an inability to reproduce naturally after the previous birth of a child, suggesting a progressive deterioration of semen quality. Semen analysis showed necrospermia in both patients, and transrectal ultrasound revealed marked dilatation of the seminal vesicles bilaterally. The main cause of secondary infertility in male patients with ADPKD is sperm death resulting from progressive dilatation of seminal vesicles. Further research is needed on the appropriate follow-up schedule for men with ADPKD who desire to reproduce naturally. (Source: CEN Case Reports)
Source: CEN Case Reports - April 8, 2024 Category: Urology & Nephrology Source Type: research
Genetics of cystogenesis in base-edited human organoids reveal therapeutic strategies for polycystic kidney disease
Cell Stem Cell. 2024 Apr 4;31(4):537-553.e5. doi: 10.1016/j.stem.2024.03.005.ABSTRACTIn polycystic kidney disease (PKD), microscopic tubules expand into macroscopic cysts. Among the world's most common genetic disorders, PKD is inherited via heterozygous loss-of-function mutations but is theorized to require additional loss of function. To test this, we establish human pluripotent stem cells in allelic series representing four common nonsense mutations, using CRISPR base editing. When differentiated into kidney organoids, homozygous mutants spontaneously form cysts, whereas heterozygous mutants (original or base corrected)...
Source: Cell Stem Cell - April 5, 2024 Category: Stem Cells Authors: Courtney E Vishy Chardai Thomas Thomas Vincent Daniel K Crawford Matthew M Goddeeris Benjamin S Freedman Source Type: research
Genetics of cystogenesis in base-edited human organoids reveal therapeutic strategies for polycystic kidney disease
Cell Stem Cell. 2024 Apr 4;31(4):537-553.e5. doi: 10.1016/j.stem.2024.03.005.ABSTRACTIn polycystic kidney disease (PKD), microscopic tubules expand into macroscopic cysts. Among the world's most common genetic disorders, PKD is inherited via heterozygous loss-of-function mutations but is theorized to require additional loss of function. To test this, we establish human pluripotent stem cells in allelic series representing four common nonsense mutations, using CRISPR base editing. When differentiated into kidney organoids, homozygous mutants spontaneously form cysts, whereas heterozygous mutants (original or base corrected)...
Source: Cell Stem Cell - April 5, 2024 Category: Stem Cells Authors: Courtney E Vishy Chardai Thomas Thomas Vincent Daniel K Crawford Matthew M Goddeeris Benjamin S Freedman Source Type: research
Genetics of cystogenesis in base-edited human organoids reveal therapeutic strategies for polycystic kidney disease
Cell Stem Cell. 2024 Apr 4;31(4):537-553.e5. doi: 10.1016/j.stem.2024.03.005.ABSTRACTIn polycystic kidney disease (PKD), microscopic tubules expand into macroscopic cysts. Among the world's most common genetic disorders, PKD is inherited via heterozygous loss-of-function mutations but is theorized to require additional loss of function. To test this, we establish human pluripotent stem cells in allelic series representing four common nonsense mutations, using CRISPR base editing. When differentiated into kidney organoids, homozygous mutants spontaneously form cysts, whereas heterozygous mutants (original or base corrected)...
Source: Cell Stem Cell - April 5, 2024 Category: Stem Cells Authors: Courtney E Vishy Chardai Thomas Thomas Vincent Daniel K Crawford Matthew M Goddeeris Benjamin S Freedman Source Type: research
Genetics of cystogenesis in base-edited human organoids reveal therapeutic strategies for polycystic kidney disease
Cell Stem Cell. 2024 Apr 4;31(4):537-553.e5. doi: 10.1016/j.stem.2024.03.005.ABSTRACTIn polycystic kidney disease (PKD), microscopic tubules expand into macroscopic cysts. Among the world's most common genetic disorders, PKD is inherited via heterozygous loss-of-function mutations but is theorized to require additional loss of function. To test this, we establish human pluripotent stem cells in allelic series representing four common nonsense mutations, using CRISPR base editing. When differentiated into kidney organoids, homozygous mutants spontaneously form cysts, whereas heterozygous mutants (original or base corrected)...
Source: Cell Stem Cell - April 5, 2024 Category: Stem Cells Authors: Courtney E Vishy Chardai Thomas Thomas Vincent Daniel K Crawford Matthew M Goddeeris Benjamin S Freedman Source Type: research
Inhibition of pannexin ‐1 does not restore electrolyte balance in precystic Pkd1 knockout mice
AbstractMutations inPKD1 andPKD2 cause autosomal dominant polycystic kidney disease (ADPKD), which is characterized by the formation of fluid-filled cysts in the kidney. In a subset of ADPKD patients, reduced blood calcium (Ca2+) and magnesium (Mg2+) concentrations are observed. As cystic fluid contains increased ATP concentrations and purinergic signaling reduces electrolyte reabsorption, we hypothesized that inhibiting ATP release could normalize blood Ca2+ and Mg2+ levels in ADPKD. Inducible kidney-specificPkd1 knockout mice (iKsp-Pkd1−/−) exhibit hypocalcemia and hypomagnesemia in a precystic stage and show increas...
Source: Physiological Reports - April 2, 2024 Category: Physiology Authors: Wouter H. van Megen,
Teun J. van Houtert,
Caro Bos,
Dorien J. M. Peters,
Jeroen H. F. de Baaij,
Joost G. J. Hoenderop Tags: ORIGINAL ARTICLE Source Type: research
