Treating incontinence by injecting muscle stem cells

This not-yet-available in the US treatment for urinary incontinence may be of interest to many in the group…

Beth (with multiple system atrophy)) had another interesting post recently on an MSA-related list. I’ve gotten her permission again to copy it below.

She includes an abstract from a 5/21/06 American Urological Association meeting. The abstract summarizes two clinical studies done in Austria and Canada on injecting muscle stem cells to treat urinary incontinence. Roger Dmochowski, MD, a professor with the Dept of Urology at Vanderbilt University in Nashville, moderated a press conference on urinary incontinence at the meeting. He said two interesting things:

* “The technique is minimally invasive compared to surgical treatments for urinary incontinence. Once it gets traction, it could go rapidly into the practice arena.”

* Some larger studies will be beginning very soon in the United States.

If you want to keep an eye out for possible trials in the US, you can: 1) watch and search on clinicaltrials.org, using “urinary incontinence” as the search term, 2) watch Medscape’s weekly newsletters, and 3) go to a medical library or go online to review announcements put out by major urology journals.

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From: Beth Klitch
Date: Tue May 30, 2006 6:01pm(PDT)
Subject: Exciting new treatment for urinary incontinence – Injection of muscle stem cells

Urinary incontinence is another common condition that we MSA patients experience. Some of us respond to medications such as Flomax that reduce the bladder spasms that can cause urge incontinence. Some of us may undergo surgery to have devices such as Medtronic’s InterStim device implanted to send electrical signals to the sacral nerves that help stimulate the bladder to contract. Many more of us find ourselves isolated or fearful of incontinence accidents and thus we pass up opportunities to travel outside our homes or to visit friends.

Earlier this month, the American Urological Association met and heard reports about a wide range of topics that affect the urinary tract. I have included an extended summary of some exciting research that is underway to treat and actually cure urinary incontinence. Note that the first two clinical studies were performed in Austria and Canada and that larger trials are planned for the United States in upcoming months. This may be an opportunity to volunteer to take part in a clinical trial that has high potential to improve the quality of our lives. Also note that the results were significantly better for women than men and that there are some risks to any surgical procedures, even ones that are minimally invasive.

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May 22, 2006 (Atlanta) ­ Injection of muscle stem cells into the suburethral mucosa may be effective for the treatment of urinary incontinence, according to findings from 2 clinical studies. Hannes Strasser, MD, from the Universitatsklinik fur Urologie, Medizinische Universitat Innsbruck, Austria, and colleagues reported their findings here at the American Urological Association 2006 Annual Meeting.

Injecting stem cells into the urethral submucosa is expected to alleviate atrophy of the submucosa by potentially boosting the contractility of the muscle tissue and improving urethral function. In the study, a total of 130 patients (45 men and 85 women) with stress or mixed urinary incontinence were treated with transurethral ultrasound­guided injections. Patients were aged 36 to 85 years. Changes in morphology and function of the urethra and rhabdosphincter and quality of life were evaluated.

While under local anesthesia, patients had small skeletal muscle biopsies taken from their upper arm. Cells from the sample were cultured, and fibroblasts were eventually mixed with about 2.5 mL of collagen, which served as carrier material. With the aid of a transurethral ultrasound probe and injection device, the fibroblasts were introduced into the urethral submucosa. The myoblasts were directly injected into the rhabdosphincter to reconstruct the muscle.

Urinary incontinence was cured after injection of stem cells in 111 (79 women, 32 men) of the 130 patients. Therapy was able to increase the thickness of the urethra and the rhabdosphincter as well as increase the activity and contractility of the rhabdosphincter. An additional 17 patients experienced an improvement but not complete relief of incontinence.

Significant improvements in quality of life were also observed after treatment, and the therapy appeared to be well tolerated. No adverse effects or complications were observed. Dr. Strasser noted that further follow-up indicated that 1 patient had a major complication ­ a perforation in a male patient who had undergone several surgeries and radiation therapy.

According to Dr. Strasser, the efficacy of this technique is better in women than men, possibly for 2 reasons: the injection is easier in women due to the shorter length of the urethra. The second is that after radical prostatectomy in men, changes such as scarring can take place in the urethra. “In females the efficacy rate is more than 90%, whereas in males the efficacy rate is about 72% to 73%,” he told Medscape.

The therapeutic effect appeared to be long-lasting. “The full effect of the therapy takes about 3 to 4 weeks to achieve, whereas other injectable therapies can take effect immediately,” he said. “However, the vast majority of patients who do well 3 months after therapy remain stable. These patients are still continent, meaning they don’t need pads.”

A smaller, North American study evaluating a similar procedure was reported by Lesley K. Carr, MD, from the University of Toronto, Ontario, Canada, and colleagues. Six women, aged 41 to 66 years, with stress urinary incontinence, were treated with either a trans- or periurethral injection technique; one of the patients was reinjected after 6 months.

Skeletal muscle tissue was taken from each patient with a needle biopsy technique. Muscle-derived cells were then isolated and expanded in culture. After at least 1 month of follow-up, no improvement was observed in patients treated with a smaller (8 mm) cystoscopic injection needle. However, 2 subsequent transurethral injections using a longer needle (10 mm) and the 2 periurethral injections did result in improvement in 4 patients, who all reported an improvement in quality of life.

“We hypothesize that the injected muscle-derived cells differentiated into new muscle fibers and improved muscle function, but the exact mechanisms of these actions are still being investigated,” note Dr. Carr and colleagues in their abstract. “Improvements to the delivery technique may have contributed to a greater success rate in the most recently injected patients.” Again, no adverse effects were noted.

Roger Dmochowski, MD, a professor with the Department of Urology at Vanderbilt University in Nashville, Tennessee, noted that the results seen with this technique are “very encouraging,” although he pointed out that various injection techniques and different types of cells are being studied, “making it difficult to compare results.”

Several centers in Europe are experimenting with autologous muscle stem cell injection, and some larger studies will be beginning very soon in the United States, noted Dr. Dmochowski, who moderated a press conference on urinary incontinence at the meeting. “The technique is minimally invasive compared to surgical treatments for urinary incontinence,” Dr. Dmochowski added. “Once it gets traction, it could go rapidly into the practice arena.”

AUA 2006 Annual Meeting: Abstracts 328 and 1284. Presented May 21, 2006.