Autologous muscle-derived cells may treat stress urinary incontinence

LINTHICUM, MD, 28 april 2009–Researchers have confirmed that transplanting autologous muscle-derived cells (AMDC) into the bladder is safe at a wide range of doses and significantly improves symptoms and quality of life in patients with stress urinary incontinence. The study was presented at the 104th Annual Scientific Meeting of the American Urological Association (AUA) and showed that the injection of muscle-derived cells was well tolerated and significantly improved symptoms.

Researchers conducted two study phases on the efficacy and safety of muscle-derived cell transplantation. In the study phases, which are ongoing, 29 women (mean age of 49.5), whose stress urinary incontinence symptoms had not improved within a year of standard therapy, received cystoscope-assisted periurethral cell injections. At the three month follow-up appointment, participants could elect a second injection of the same dose. Follow-up occurred at one, three, six and 12 months after the last injection. Clinical outcomes were evaluated with a pad weight test, a voiding diary and validated quality of life questionnaires. In the first, double-blind phase, 20 patients were randomized into five groups to receive one, two, four, eight or 16 x 106 AMDCs. In the second, single-blind phase, nine patients were randomized into three groups to receive 32, 64, or 128 x 106 AMDCs.

Results showed that 86.2 percent of the 29 patients elected a second injection. To date, 17 patients have reached the 12-month follow-up appointment. No serious adverse events have been encountered. Minor events occurred at similar rates among all dose groups and included pain and bruising at the muscle biopsy site, pain at the injection site, mild and self-limiting urinary retention and urinary tract infection. One patient experienced notably worsened incontinence. Quality of life measures improved in 68 percent of patients three months after the first injection and in 67 percent of patients three months after the second injection. Symptoms improved in 61 percent of patients at three months after the first injection and three months after the second injection. Urinary leaks were reduced after both injections. At 12 months, 13 of 17 patients (76.5 percent) reported an overall reduction in stress leaks and urgency compared to baseline; four reported no leaks.

"This study confirms that autologous muscle-derived cells constitute a safe and effective treatment for incontinence at various dosages," said Anthony Atala, MD, an AUA spokesman. "It is important to note that this therapy has few side effects and seems to improve symptoms for most patients in whom other therapies failed."

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NOTE TO REPORTERS: Experts are available to discuss this study outside normal briefing times. To arrange an interview with an expert, please contact the AUA Communications Office at the number above or e-mail Lacey Dean at LDean@AUAnet.org.

Carr, L; Herschorn, S, Birch, C; Murphy, M; Robert, M; Jankowski, R; Pruchnic, R; Wagner, D; Chancellor, M. Autologous muscle-derived cells as therapy for stress urinary incontinence: a randomized, blinded multi-dose study. J Urol, suppl. 2009: 181, 4, abstract 1526.

AUA: Autologous Cell Transplants Show Promise for Stress Urinary Incontinence

By Charles Bankhead
ORLANDO, 28 may 2008-- For stress urinary incontinence, the use of transplanted autologous muscle-derived cells has led to significant and durable symptom improvement, investigators reported here.
Of 177 patients followed for up to two years, fewer than 10% of women and 30% of men required absorbent pads, Hannes Strasser, M.D., of the Medical University of Innsbruck in Austria, said at the American Urological Association meeting.
"The procedure is safe and minimally invasive," said Dr. Strasser. "Ultrasonography-guided injection of autologous cells has been very effective and also very precise, which is of utmost importance."
Since April 2004, Dr. Strasser and colleagues have used cell transplantation to treat 65 men and 112 women, starting with removal of a small amount of muscle from the patient's upper arm. Myoblasts and fibroblasts are grown in culture for six to eight weeks. The fibroblasts are mixed with a small amount of collagen, which serves as a carrier and prevents cell migration.
Guided by transurethral ultrasound, the fibroblasts are injected into the urethral submucosa to treat atrophy, and the myoblasts are injected into the rhabdosphincter to effect reconstruction.
Follow-up examinations revealed thickening of the urethra and rhabdosphincter and increased contractility of the rhabdosphincter.
At baseline the women used an average of six pads daily, which decreased to one pad at two years. Dr. Strasser reported that 62.5% of the women required no pads, 28.4% used a single pad daily for precautionary reasons, and 9.1% still required multiple pads because of persistent urinary incontinence.
Most of the men had urinary incontinence secondary to treatment of prostate cancer. On average the men required about five pads daily before treatment, decreasing to 1.59 at two years. Dr. Strasser said 27.9% of the men had regained complete continence, 43.6% used a single pad daily as a precaution, and 28.5% had persistent urinary incontinence.
There were no severe treatment side effects or complications. One patient who had undergone multiple surgical procedures and radiation therapy had a bladder perforation. No patient had signs of obstruction, scars or strictures, or bulking of injected cells.
Longer follow-up is needed to confirm the safety and efficacy of the procedure, Dr. Strasser said, and a multicenter trial is needed to demonstrate replicability.
"This is not a wonder therapy that works in every incontinent patient," Dr. Strasser cautioned. "It cannot be used in patients with hypermobility or in patients with prolapse. It works very well in patients with intrinsic sphincter insufficiency."
Dr. Strasser disclosed that he has an ownership stake in Innovacell Biotechnologie GmbH.
Primary source: Journal of UrologySource reference:Strasser H, et al "Transurethral ultrasound guided injection oif autologous myo- and fibroblasts in treatment of incontinence in men: 2 year data" J Urol 2008; 179(suppl):483. Abstract 1413. Additional source: Journal of UrologySource reference: Strasser H, et al "Transsurethral ultrasound guided application of autologous myo- and fibroblasts in treatment of incontinence in women: 2 year data" J Urol 2008; 179(suppl):534. Abstract 1561.