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Article of the week: Implanting periurethral myofibres to treat incontinence

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video of Prof. René Yiou discussing his article.

If you only have time to read one article this week, it should be this one.

 

Periurethral skeletal myofibre implantation in patients with urinary incontinence and intrinsic sphincter deficiency: a phase I clinical trial

René Yiou1, Jean-Yves Hogrel8, Catherine-Marie Loche2, François-Jerome Authier3, Philippe Lecorvoisier7, Pauline Jouany4, Françoise Roudot-Thoraval5 and Jean-Pascal Lefaucheur6

1Hôpital Henri Mondor, Service d’Urologie and CRCDC, 2Hôpital Albert Chenevier, Service de Médecine Physique et de Réadaptation, 3Hôpital Henri Mondor, Département de Pathologie, 4Hôpital Henri Mondor, Unité de Recherche Clinique (URC), Pôle Recherche Clinique et Santé Publique, 5Hôpital Henri Mondor, Département de Santé Publique, Pôle Recherche Clinique et Santé Publique, UPEC, 6Hôpital Henri Mondor, Service de Physiologie – Explorations Fonctionnelles, Université Paris-Est, Faculté de Médecine, APHP, 7Hôpital Henri Mondor, INSERM, Créteil, and 8Université Paris 6, UMR S974, INSERM U974, CNRS UMR 7215, GH Pitié-Salpêtrière, Institut de Myologie, Paris, France

This open-label nonrandomized phase I clinical trial was registered on clinicalTrials.gov (#NCT00472069)

OBJECTIVES

• To assess the safety of periurethral myofibre implantation in patients with urinary incontinence due to intrinsic sphincter deficiency (ISD).

• To assess the resulting myogenic process and effects on urinary continence.

PATIENTS AND METHODS

• An open-label non-randomised phase I clinical trial was conducted in five men and five women with ISD (mean age, 62.5 years).

• A free muscle strip from the patient’s gracilis muscle was implanted around the urethra as a means to deliver locally myofibres and muscle precursor cells (MPCs).

• Patients were assessed for collection formation and incomplete bladder emptying.

• The maximum urethral closure pressure (MUCP) and concomitant periurethral electromyographic (EMG) activity were recorded before surgery and 1 and 3 months after surgery. Continence was assessed using the 24-h pad test and self-completed questionnaires, for 12 months.

RESULTS

• There were no serious side-effects.

• Continence improved significantly during the 12-month follow-up in four of the five women, including two who recovered normal continence. In the women, MUCP increased two-fold and de novo EMG periurethral activity was recorded. In the men, MUCP and EMG recordings showed similar improvements but the effect on continence was moderate.

• The few patients enrolled could affect these results.

CONCLUSIONS

• This is the first report of a one-step procedure for transferring autologous MPCs via myofibre implantation in patients with ISD.

• EMG and urodynamic assessments showed improvement of periurethral muscle activity.

• Further work is needed to confirm and improve the therapeutic efficiency of this procedure.

 

Read Previous Articles of the Week

 

Editorial: A step toward simplicity

Although effective, current treatments of stress urinary incontinence (SUI) can be viewed as palliatives, as they do not regenerate the normal function of the urethral sphincter. Cell therapy pretends to do so.

Mesenchymal-derived stem cells, isolated from bone marrow, striated muscle or fat have been investigated. Transurethral injection of striated muscle-derived stem cells (MDSCs) has been the most studied technique in human. Although results were encouraging, the need for pre-implantation cell expansion to provide a sufficient amount of cells has two major drawbacks. First, the need for a complex long and expensive process of cell biology to treat a patient precludes diffusion of such a technique. Secondly, cell culture and manipulation are known to affect survival and myogenic potential of MDSCs.

After they first demonstrated in pigs, that an autologous graft of a striated muscle piece around the urethra resulted in degeneration of mature myocytes and an activation of satellite cells, which differentiated in well-oriented myotubes with synapses and contractility, for the first time, Yiou et al. report in BJUI clinical data on striated muscle cells used as a source of stem cells to repair the urethral sphincter without cell expansion in a ‘one-time’ procedure.

The step is remarkable and is a step toward simplicity. It has to be kept in mind that SUI pathophysiology does not only suppose a damaged muscle. Denervation is another mechanism as suggested by the observation of longer activation latency in the urethral sphincter before stress, cough or sneeze in incontinent female patients without neurological disease. Urethral fibrosis is implicated in post-prostatectomy SUI or after urethral complication of a first anti-incontinence procedure.

There is still need for an extensive and subtler understanding of the mechanisms leading to different forms of SUI. Cell therapy will find its specific indications among these different forms of SUI. Combined cell therapy approaches (muscle based, fat based and other) may be the way to regenerate the whole function of the urethral sphincter.

 

Gilles Karsenty*
*Aix-Marseille University, and Department of Urology and Kidney Transplantation, La Conception Hospital, Marseille, France

Read the full article

Video: Treating intrinsic sphincter deficiency with myofibre implantation

 

 

Periurethral skeletal myofibre implantation in patients with urinary incontinence and intrinsic sphincter deficiency: a phase I clinical trial

René Yiou1, Jean-Yves Hogrel8, Catherine-Marie Loche2, François-Jerome Authier3, Philippe Lecorvoisier7, Pauline Jouany4, Françoise Roudot-Thoraval5 and Jean-Pascal Lefaucheur6

1Hôpital Henri Mondor, Service d’Urologie and CRCDC, 2Hôpital Albert Chenevier, Service de Médecine Physique et de Réadaptation, 3Hôpital Henri Mondor, Département de Pathologie, 4Hôpital Henri Mondor, Unité de Recherche Clinique (URC), Pôle Recherche Clinique et Santé Publique, 5Hôpital Henri Mondor, Département de Santé Publique, Pôle Recherche Clinique et Santé Publique, UPEC, 6Hôpital Henri Mondor, Service de Physiologie – Explorations Fonctionnelles, Université Paris-Est, Faculté de Médecine, APHP, 7Hôpital Henri Mondor, INSERM, Créteil, and 8Université Paris 6, UMR S974, INSERM U974, CNRS UMR 7215, GH Pitié-Salpêtrière, Institut de Myologie, Paris, France

This open-label nonrandomized phase I clinical trial was registered on clinicalTrials.gov (#NCT00472069)

OBJECTIVES

• To assess the safety of periurethral myofibre implantation in patients with urinary incontinence due to intrinsic sphincter deficiency (ISD).

• To assess the resulting myogenic process and effects on urinary continence.

PATIENTS AND METHODS

• An open-label non-randomised phase I clinical trial was conducted in five men and five women with ISD (mean age, 62.5 years).

• A free muscle strip from the patient’s gracilis muscle was implanted around the urethra as a means to deliver locally myofibres and muscle precursor cells (MPCs).

• Patients were assessed for collection formation and incomplete bladder emptying.

• The maximum urethral closure pressure (MUCP) and concomitant periurethral electromyographic (EMG) activity were recorded before surgery and 1 and 3 months after surgery. Continence was assessed using the 24-h pad test and self-completed questionnaires, for 12 months.

RESULTS

• There were no serious side-effects.

• Continence improved significantly during the 12-month follow-up in four of the five women, including two who recovered normal continence. In the women, MUCP increased two-fold and de novo EMG periurethral activity was recorded. In the men, MUCP and EMG recordings showed similar improvements but the effect on continence was moderate.

• The few patients enrolled could affect these results.

CONCLUSIONS

• This is the first report of a one-step procedure for transferring autologous MPCs via myofibre implantation in patients with ISD.

• EMG and urodynamic assessments showed improvement of periurethral muscle activity.

• Further work is needed to confirm and improve the therapeutic efficiency of this procedure.

 

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