title: Ciliotherapy: a novel intervention in polycystic kidney disease.
abstract: BACKGROUND
  Ciliopathies are a group of diseases associated with abnormal structure or function of primary cilia. Ciliopathies include polycystic kidney disease (PKD), a pathology associated with vascular hypertension. We previously showed that cilia length regulates cilia function, and cilia function is required for nitric oxide (NO) biosynthesis in endothelial cells. Because patients with PKD show abnormal sensory cilia function, the aim of our current study was to search for a targeted therapy focused on primary cilia, which we refer to as 'ciliotherapy'.
  
  
  RESULTS
  In the present studies, our in vitro analyses refined fenoldopam as an equipotent and more specific dopaminergic agonist to regulate cilia length and function. Our in vivo studies indicated that fenoldopam increased cilia length and serum NO thereby reducing blood pressure in a PKD mouse model. Our crossover, multicenter, double-blind and placebo-controlled clinical study further indicated that cilia-targeting therapy showed an overall reduction in mean arterial pressure in PKD patients.
  
  
  CONCLUSIONS
  Overall, our studies provide the first evidence of ciliotherapy as an innovative intervention in patients with abnormal primary cilia.
authors.affiliation: Center for Hypertension and Personalized Medicine, University of Toledo, Health Science Building, Room 312, 3000 Arlington Ave., Toledo, OH 43614, USA ; Department of Pharmacology, University of Toledo, Health Education Building, Room 274, 3000 Arlington Ave., Toledo, OH 43614, USA ; College of Pharmacy, University of Baghdad, Bab-Almoadhum 14026, Baghdad, Iraq.
authors.forename: Sarmed H
authors.initials: SH
authors.lastname: Kathem
authors.affiliation: Center for Hypertension and Personalized Medicine, University of Toledo, Health Science Building, Room 312, 3000 Arlington Ave., Toledo, OH 43614, USA ; Department of Pharmacology, University of Toledo, Health Education Building, Room 274, 3000 Arlington Ave., Toledo, OH 43614, USA.
authors.forename: Ashraf M
authors.initials: AM
authors.lastname: Mohieldin
authors.affiliation: Center for Hypertension and Personalized Medicine, University of Toledo, Health Science Building, Room 312, 3000 Arlington Ave., Toledo, OH 43614, USA ; Department of Pharmacology, University of Toledo, Health Education Building, Room 274, 3000 Arlington Ave., Toledo, OH 43614, USA.
authors.forename: Shakila
authors.initials: S
authors.lastname: Abdul-Majeed
authors.affiliation: College of Pharmacy, University of Baghdad, Bab-Almoadhum 14026, Baghdad, Iraq.
authors.forename: Sajida H
authors.initials: SH
authors.lastname: Ismail
authors.affiliation: Kidney Disease and Transplant Center, Medical City Complex, Bab-Almoadhum 14026, Baghdad, Iraq.
authors.forename: Qaiss H
authors.initials: QH
authors.lastname: Altaei
authors.affiliation: Alkadhumia Academic Hospital, Bab-Almoadhum 14026, Baghdad, Iraq.
authors.forename: Ibrahim K
authors.initials: IK
authors.lastname: Alshimmari
authors.affiliation: Alkadhumia Academic Hospital, Bab-Almoadhum 14026, Baghdad, Iraq.
authors.forename: Mohanned M
authors.initials: MM
authors.lastname: Alsaidi
authors.affiliation: Alkadhumia Academic Hospital, Bab-Almoadhum 14026, Baghdad, Iraq.
authors.forename: Hussein
authors.initials: H
authors.lastname: Khammas
authors.affiliation: Pharmaceutical & Biomedical Sciences, California Northstate University, 10811 International Drive, Rancho Cordova, CA 95670, USA.
authors.forename: Andromeda M
authors.initials: AM
authors.lastname: Nauli
authors.affiliation: Center for Hypertension and Personalized Medicine, University of Toledo, Health Science Building, Room 312, 3000 Arlington Ave., Toledo, OH 43614, USA.
authors.forename: Bina
authors.initials: B
authors.lastname: Joe
authors.affiliation: Center for Hypertension and Personalized Medicine, University of Toledo, Health Science Building, Room 312, 3000 Arlington Ave., Toledo, OH 43614, USA ; Department of Pharmacology, University of Toledo, Health Education Building, Room 274, 3000 Arlington Ave., Toledo, OH 43614, USA.
authors.forename: Surya M
authors.initials: SM
authors.lastname: Nauli
keywords: Blood pressure; Chemosensor; Fluid-shear stress; Mechanosensor; Mechanotransduction; Primary cilium
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