Journal article
Gene Therapeutic Reversal of Peripheral Olfactory Impairment in Bardet-Biedl Syndrome
Molecular therapy, Vol.25(4), pp.904-916
04/05/2017
DOI: 10.1016/j.ymthe.2017.02.006
PMCID: PMC5383630
PMID: 28237838
Abstract
Olfactory dysfunction is a pervasive but underappreciated health concern that affects personal safety and quality of life. Patients with olfactory dysfunctions have limited therapeutic options, particularly those involving congenital diseases. Bardet-Biedl syndrome (BBS) is one such disorder, where olfactory loss and other symptoms manifest from defective cilium morphology and/or function in various cell types/tissues. Olfactory sensory neurons (OSNs) of BBS mutant mice lack the capacity to build/maintain cilia, rendering the cells incapable of odor detection. Here we examined OSN cilium defects in Bbs1 mutant mice and assessed the utility of gene therapy to restore ciliation and function in young and adult mice. Bbs1 mutant mice possessed short residual OSN cilia in which BBSome protein trafficking and odorant detection were defective. Gene therapy with an adenovirus-delivered wild-type Bbs1 gene restored OSN ciliation, corrected BBSome cilium trafficking defects, and returned acute odor responses. Finally, using clinically approved AAV serotypes, we demonstrate, for the first time, the capacity of AAVs to restore ciliation and odor detection in OSNs of Bbs1 mutants. Together, our data demonstrate that OSN ciliogenesis can be promoted in differentiated cells of young and adult Bbs1 mutants and highlight the potential of gene therapy as a viable restorative treatment for congenital olfactory disorders.
Olfactory dysfunction is a health concern with limited therapeutic options, particularly in congenital disorders such as Bardet-Biedl syndrome (BBS). In this issue of Molecular Therapy, Williams et al. (2017) demonstrated the utility of gene therapy to restore olfactory function in young and adult mice with BBS.
Details
- Title: Subtitle
- Gene Therapeutic Reversal of Peripheral Olfactory Impairment in Bardet-Biedl Syndrome
- Creators
- Corey L Williams - Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610, USACedric R Uytingco - Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610, USAWarren W Green - Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610, USAJeremy C McIntyre - Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610, USAKirill Ukhanov - Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610, USAArthur D Zimmerman - Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610, USADana T Shively - Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610, USALian Zhang - Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610, USADarryl Y Nishimura - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USAVal C Sheffield - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USAJeffrey R Martens - Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610, USA
- Resource Type
- Journal article
- Publication Details
- Molecular therapy, Vol.25(4), pp.904-916
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.ymthe.2017.02.006
- PMID
- 28237838
- PMCID
- PMC5383630
- ISSN
- 1525-0016
- eISSN
- 1525-0024
- Language
- English
- Date published
- 04/05/2017
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984065483902771
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