title: Does Reduction of Number of Intradetrusor Injection Sites of aboBoNTA (Dysport®) Impact Efficacy and Safety in a Rat Model of Neurogenic Detrusor Overactivity?
abstract: Intradetrusor injections of Botulinum toxin A-currently onabotulinumtoxinA-is registered as a second-line treatment to treat neurogenic detrusor overactivity (NDO). The common clinical practice is 30 × 1 mL injections in the detrusor; however, protocols remain variable and standardization is warranted. The effect of reducing the number of injection sites of Dysport(®) abobotulinumtoxinA (aboBoNTA) was assessed in the spinal cord-injured rat (SCI). Nineteen days post-spinalization, female rats received intradetrusor injections of saline or aboBoNTA 22.5 U distributed among four or eight sites. Two days after injection, continuous cystometry was performed in conscious rats. Efficacy of aboBoNTA 22.5 U was assessed versus aggregated saline groups on clinically-relevant parameters: maximal pressure, bladder capacity, compliance, voiding efficiency, as well as amplitude, frequency, and volume threshold for nonvoiding contractions (NVC). AboBoNTA 22.5 U significantly decreased maximal pressure, without affecting voiding efficiency. Injected in four sites, aboBoNTA significantly increased bladder capacity and compliance while only the latter when in eight sites. AboBoNTA significantly reduced NVC frequency and amplitude. This preclinical investigation showed similar inhibiting effects of aboBoNTA despite the number of sites reduction. Further studies are warranted to optimize dosing schemes to improve the risk-benefit ratio of BoNTA-based treatment modalities for NDO and further idiopathic overactive bladder.
authors.affiliation: Pelvipharm, 2 avenue de la source de la Bièvre, Bâtiment Simone Veil, Université de Versailles-Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux 78180, France. a.lemaux@pelvipharm.com.|Unité de Formation et de Recherche des Sciences de la Santé, Université de Versailles-Saint-Quentin-en-Yvelines, Institut National de la Santé Et de la Recherche Médicale U1179, Montigny-le-Bretonneux 78180, France. a.lemaux@pelvipharm.com.
authors.forename: Amélie
authors.initials: A
authors.lastname: Huynh Le Maux
authors.affiliation: IPSEN Innovation, 5 avenue du Canada, Les Ulis 91140, France. bernadette.pignol@ipsen.com.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Pignol
authors.affiliation: Pelvipharm, 2 avenue de la source de la Bièvre, Bâtiment Simone Veil, Université de Versailles-Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux 78180, France. d.behr.roussel@pelvipharm.com.|Unité de Formation et de Recherche des Sciences de la Santé, Université de Versailles-Saint-Quentin-en-Yvelines, Institut National de la Santé Et de la Recherche Médicale U1179, Montigny-le-Bretonneux 78180, France. d.behr.roussel@pelvipharm.com.
authors.forename: Delphine
authors.initials: D
authors.lastname: Behr-Roussel
authors.affiliation: IPSEN Innovation, 5 avenue du Canada, Les Ulis 91140, France. jean-luc.blachon@ipsen.com.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Blachon
authors.affiliation: IPSEN Innovation, 5 avenue du Canada, Les Ulis 91140, France. pierre-et.chabrier@ipsen.com.
authors.forename: Pierre-Etienne
authors.initials: PE
authors.lastname: Chabrier
authors.affiliation: Pelvipharm, 2 avenue de la source de la Bièvre, Bâtiment Simone Veil, Université de Versailles-Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux 78180, France. s.compagnie@pelvipharm.com.|Unité de Formation et de Recherche des Sciences de la Santé, Université de Versailles-Saint-Quentin-en-Yvelines, Institut National de la Santé Et de la Recherche Médicale U1179, Montigny-le-Bretonneux 78180, France. s.compagnie@pelvipharm.com.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Compagnie
authors.affiliation: IPSEN Innovation, 5 avenue du Canada, Les Ulis 91140, France. philippe.picaut@ipsen.com.
authors.forename: Philippe
authors.initials: P
authors.lastname: Picaut
authors.affiliation: Pelvipharm, 2 avenue de la source de la Bièvre, Bâtiment Simone Veil, Université de Versailles-Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux 78180, France. j.bernabe@pelvipharm.com.|Unité de Formation et de Recherche des Sciences de la Santé, Université de Versailles-Saint-Quentin-en-Yvelines, Institut National de la Santé Et de la Recherche Médicale U1179, Montigny-le-Bretonneux 78180, France. j.bernabe@pelvipharm.com.
authors.forename: Jacques
authors.initials: J
authors.lastname: Bernabé
authors.affiliation: Unité de Formation et de Recherche des Sciences de la Santé, Université de Versailles-Saint-Quentin-en-Yvelines, Institut National de la Santé Et de la Recherche Médicale U1179, Montigny-le-Bretonneux 78180, France. francois.giuliano@uvsq.fr.|Assistance Publique-Hôpitaux de Paris, Neuro-Uro-Andrology, Raymond Poincaré Hospital, Department of Physical Medicine and Rehabilitation, Garches 92380, France. francois.giuliano@uvsq.fr.
authors.forename: François
authors.initials: F
authors.lastname: Giuliano
authors.affiliation: Unité de Formation et de Recherche des Sciences de la Santé, Université de Versailles-Saint-Quentin-en-Yvelines, Institut National de la Santé Et de la Recherche Médicale U1179, Montigny-le-Bretonneux 78180, France. pierre.denys@rpc.aphp.fr.|Assistance Publique-Hôpitaux de Paris, Neuro-Uro-Andrology, Raymond Poincaré Hospital, Department of Physical Medicine and Rehabilitation, Garches 92380, France. pierre.denys@rpc.aphp.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Denys
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D007273:Injections, Intramuscular; D009465:Neuromuscular Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A; C542869:abobotulinumtoxinA
keywords: abobotulinumtoxinA; injection procedure; injection site number; neurogenic detrusor overactivity; spinal-cord injury