A New Therapeutic Strategy for Urethral Sphincter Insufficiency
A New Therapeutic Strategy for Urethral Sphincter Insufficiency
Stress urinary incontinence is a frequent condition that can be caused by urethral sphincter
 insufficiency and results in a dramatic deterioration of the quality of life. We developed a
 new therapeutic strategy for stress urinary incontinence based on the implantation myofibers
 with their satellite cells in the urethra. The aim of this procedure is to generate
 functional tissue acting like a new sphincter in the urethra
stress urinary incontinence is a frequent condition that can be caused by urethral sphincter
 insufficiency and results in a dramatic deterioration of the quality of life. We developed a
 new therapeutic strategy for stress urinary incontinence based on the implantation myofibers
 with their satellite cells. The principle of this procedure relies on the activation in vivo
 of the satellite cells present around each myofibers. Satellite cell activation is
 concomitant with myofiber death that occurs after their implantation. Activated satellite
 proliferate and fuse to form myotubes replacing the parental myofibers thus leading to the
 reconstitution of the muscle mass that was initially implanted. Preliminary studies in the
 pig showed the regenerated muscle tissue in the urethra was innervated by urethral nerves and
 developed tonic contractions acting like a new sphincter. This procedure does not include a
 phase of satellite cell amplification ex vivo, as standard methods of satellite cell
 transfer, and rather relies on the natural myogenic capacities of these cells. Thus, the
 procedure of cell transfer into the urethra is considerably simplified and can be performed
 in one step in the operating room.This therapeutic strategy could represent an alternative to
 the artificial urinary sphincter.
Inclusion Criteria:

 -  Men or women from 40 to 75 years old, suffering from urinary incontinence since at
 least 6 months and candidate for a surgical treatment (artificial urinary sphincter,
 synthetic compressive tapes or adjustable balloons).

 The myofiber implantation procedure will be proposed after failure of pelvic floor
 exercises.

 -  The observation of urine leakage during cough in consultation or during urodynamic
 (with absence of abnormal vesical contraction) and a score MHU > 2 (domain of stress
 urinary incontinence) will be considered as the main diagnostic criteria.

 -  An urethral closure pressure lower than 40 cm H20 will be the main urodynamic
 diagnostic criterion

 -  For women: a negative BONNEY test, and Qtip test<40° (c.f. annex) demonstrating the
 absence of vesica-urethral hypermobility.

 24 hours Pad test > 20g.

 Exclusion Criteria:

 -  Incapacity to answer the questionnaires of evaluation.

 -  History of pelvic radiotherapy.

 -  Disorder of hemostasis.

 -  Untreated urinary infection.

 -  Genetically determined or acquired muscular disease.

 -  Neurological disorder (Parkinson's disease, multiple sclerosis, spina BIFIDA,
 medullary traumatism).

 -  The patients suffering from stress urinary incontinence due to vesica-urethral
 hypermobility (positive BONNEY test and Qtip test >40°) will not be included in the
 study because the referenced treatment is the implantation of a vaginal tape
 supporting the urethra.

 -  Incomplete vesical emptying. Residual volume > 20% of the urinated volume with a
 micturition >150cc.

 -  Dysuria: maximum urinary flow < 12 ml/sec, IPSS score>7 or score (men) or MHU dysuria
 domain none equal to 0 at woman.

 -  Vesical instability (bladder contraction > 10 cm H20 during the vesical filling of the
 cysto-manometry). bladder capacity (B3) < 300 DC.

 -  Urethral Stenosis (ureterocystoscopy).

 -  Previous surgeries for urinary incontinence do not constitute a criterion of
 exclusion.

 -  Pregnancy or intention of pregnancy throughout study. A test of pregnancy will be
 carried out with the visit of inclusion.

 -  Urethral diverticulum.