TY - JOUR
T1 - Gene therapy for overactive bladder
T2 - A review of bk-channel α-subunit gene transfer
AU - Andersson, Karl Erik
AU - Christ, George Joseph
AU - Davies, Kelvin P.
AU - Rovner, Eric S.
AU - Melman, Arnold
N1 - Funding Information:
ION-03 was supported in part by National Institute on Aging grant R44DK093279. Urovant Sciences provided funding for medical writing and editorial support, which was provided by The Curry Rockefeller Group, LLC.
Funding Information:
Medical writing and editorial support was provided to the authors by The Curry Rockefeller Group, LLC, T arrytown, NY , and was funded by Urovant Sciences.
Publisher Copyright:
© 2021 Andersson et al. terms.php and incorporate.
PY - 2021
Y1 - 2021
N2 - A need exists for local (ie, bladder-specific) interventions to treat overactive bladder (OAB) with low risk of unwanted postprocedural outcomes. Gene therapy targeted to leverage endogenous physiology in bladder cells may assist in restoring normal cell and organ function. Herein, we review the potential promise of gene therapy for treating OAB, focusing on gene transfer of URO-902, a non-viral naked plasmid DNA expressing the big potassium (BK) channel. We searched PubMed for articles concerning functional aspects of the BK channel and its potential use for gene transfer as local OAB treatment. Results from preclinical, phase 1, and phase 2 studies of URO-902 for erectile dysfunction and phase 1 studies of URO-902 for OAB are included. The BK channel has been extensively studied; however, URO-902 is the first gene therapy used in clinical trials directed toward treating OAB via the BK channel. In both URO-902 studies, there were no serious adverse events considered treatment related and no adverse events leading to early withdrawal. Both studies included secondary efficacy endpoints with promising results suggesting improvement in OAB symptoms, and quality of life, with use of URO-902 versus placebo. Gene therapy involving the BK channel, such as gene transfer with URO-902, has demonstrated promising safety and efficacy results in women with OAB. Findings warrant further investigation of the use of URO-902 for OAB treatment.
AB - A need exists for local (ie, bladder-specific) interventions to treat overactive bladder (OAB) with low risk of unwanted postprocedural outcomes. Gene therapy targeted to leverage endogenous physiology in bladder cells may assist in restoring normal cell and organ function. Herein, we review the potential promise of gene therapy for treating OAB, focusing on gene transfer of URO-902, a non-viral naked plasmid DNA expressing the big potassium (BK) channel. We searched PubMed for articles concerning functional aspects of the BK channel and its potential use for gene transfer as local OAB treatment. Results from preclinical, phase 1, and phase 2 studies of URO-902 for erectile dysfunction and phase 1 studies of URO-902 for OAB are included. The BK channel has been extensively studied; however, URO-902 is the first gene therapy used in clinical trials directed toward treating OAB via the BK channel. In both URO-902 studies, there were no serious adverse events considered treatment related and no adverse events leading to early withdrawal. Both studies included secondary efficacy endpoints with promising results suggesting improvement in OAB symptoms, and quality of life, with use of URO-902 versus placebo. Gene therapy involving the BK channel, such as gene transfer with URO-902, has demonstrated promising safety and efficacy results in women with OAB. Findings warrant further investigation of the use of URO-902 for OAB treatment.
KW - Big potassium channel
KW - Gene expression
KW - Ion channels
KW - Urinary bladder
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U2 - 10.2147/TCRM.S291798
DO - 10.2147/TCRM.S291798
M3 - Review article
AN - SCOPUS:85108188570
SN - 1176-6336
VL - 17
SP - 589
EP - 599
JO - Therapeutics and Clinical Risk Management
JF - Therapeutics and Clinical Risk Management
ER -