Francois Giuliano, Versailles Saint Quentin University, Raymond Poincaré Academic Hospital, Garches, France

Gene therapy to restore urinary continence and micturition in neurogenic detrusor overactivity due to spinal cord injury

Funded in: 2017, 2018, 2019


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Problem: Neurogenic detrusor overactivity (NDO) is a severe disabling disorder resulting in urinary incontinence and recurrent urinary infections.

Target: Vectors to inhibit the transmission of aberrant information from the bladder to the spinal cord

Goal: Change the management of NDO by restoring urinary continence and voluntary micturition

 

Restoration of urinary continence and voluntary micturition is an unmet medical need after SCI. Neurogenic detrusor overactivity (NDO) is a severe disabling disorder resulting in urinary incontinence, recurrent urinary infections and, if untreated, renal failure which can be fatal.

NDO affects the vast majority of SCI patients. In NDO, bladder afferent nerves from the bladder to the spinal cord send aberrant information to the spinal cord resulting in chaotic bladder contractions. There is also a loss of brain control on the spinal cord responsible for a lack of voluntary control on micturition.

Current NDO treatments paralyze the bladder. Intermittent bladder catheterization (5-6 times a day) is therefore mandatory for bladder emptying, which is responsible for recurrent urinary infections and for a significant decrease in quality of life by increasing disability.

We are designing, assessing and developing vectors to inhibit the transmission of aberrant information from the bladder to the spinal cord via bladder afferents without eliciting bladder paralysis. The vectors are injected into the bladder to silence bladder afferents by shutting down their intracellular machinery. Ultimately vectors will be tested for safety and efficacy in a model of paraplegia and compared to existing treatment i. e. injected botulinum toxin.

This program aims to develop a gene therapy to treat NDO without paralyzing the bladder. The neural command of micturition thus remains available for on-demand electrical stimulation by an implantable stimulator (already available in humans) to elicit micturition without bladder catheterization.

We expect to radically change the management of NDO in SCI patients by restoring urinary continence and voluntary micturition.