Sphincter Regeneration Using Autologous Muscle Derived Cells Kenneth M. Peters, MD Professor and...
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Transcript of Sphincter Regeneration Using Autologous Muscle Derived Cells Kenneth M. Peters, MD Professor and...
Sphincter Regeneration Using Autologous Muscle
Derived Cells
Kenneth M. Peters, MDProfessor and Chairman of Urology
Oakland University William Beaumont School of Medicine
Royal Oak, Michigan
From Bedside to Benchtop and Back
1. Skeletal Muscle Biopsy from Thigh
2. Cell Isolation (Processing Patented and Proprietary)
3. Expansion and Differentiation
4. Autologous Injection into Urethral Sphinchter
Potential Mechanisms of Therapeutic Benefit:• New muscle formation• Augmentation of existing muscle• Secretion of growth factors/host tissue remodeling
Single Institution Clinical Trial of Muscle-Derived Cell Injection to
Treat Stress Urinary Incontinence
Carr, Steele, Steele, Wagner, Pruchnic, Jankowski, Erickson, Huard, Chancellor
Int. Urogyencology J. 19:881-883, 2008
Clinical Trial Eight women with SUI at Sunnybrook and Women’s
Health Science Centre, Department of Urology at the University of Toronto
Protocol approved by IRB and Health Canada
The injection technique evolved during the initial set of patient
A dosage of 18-22 x 106autologous MDC was used
Results
Mean follow up 17 (range 3-24) months Improvement in SUI was seen by objective
and/or subjective measures in 5 of 8 women with 1 achieving total continence
Onset of improvement was noted between 3-8 months after injection
Carr, Steele, Steele, Wagner, Pruchnic, Jankowski, Erickson, Huard, Chancellor: IntUrogyencology J. 19:881-883, 2008
AUTOLOGOUS MUSCLE-DERIVED CELLSAS A THERAPY FOR STRESS URINARY
INCONTINENCE (SUI): A RANDOMIZED, BLINDED TRIAL
Lesley Carr, Sender Herschorn, Colin Birch, Magnus Murphy, Magali Robert,
Ronald Jankowski, Ryan Pruchnic, David Wagner, Michael Chancellor
Study Conducted at Sunnybrook Health Sciences Center & University of Calgary
Study Design
BIOPSY OF QUADRICEPS FEMORIS
IN VITRO EXPANSION OF AMDCs
CYSTOSCOPE-ASSISTED PERIURETHRAL INJECTION* OF AMDCsLOW (1, 2, 4, 8, 16x106) OR HIGH (32, 64, 128x106) DOSE
1 & 3-MO FOLLOW-UP
RE-TREATMENT?
6 & 12-MO FOLLOW-UP
REPEATIN VITRO EXPANSION
2ND TREATMENT§
7, 9, 12 & 18-MO FOLLOW-UP
NO YES
All patients were blinded to dose received.
* 9 patients received ultrasound guided injections of 16, 32, or 64x106AMDCs.
§ Mean time from 1st to 2nd injection was 161±38 days.
Baseline Patient Characteristics
Mean(range)
All Patientsn = 38
Low Dosen = 23
≤ 16 million cells
High Dosen = 15
≥ 32 million cells
Age 50(30-73)
51(41-73)
49(30-70)
3-day Stress Leaks*
4.5(0-17)
5.3(0-17)
3.3(0-9)
UDI-6§ 48(17-92)
47(17-92)
51(17-83)
IIQ-7§ 34(0-76)
32(0-57)
38(19-76)
* Although all patients met inclusion criteria, 7 patients reported no baseline stress leaks.No significant differences in baseline characteristics between low and high dose groups.
Basel
ine
1 M
3 M
7 M
9 M
12 M
18 M
Basel
ine
1 M
3 M
7 M
9 M
12 M
18 M
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1 LeakNo Leak
Patients Reporting 0 or 1 Stress Leaks Over 3 DaysDOUBLE-INJECTION PATIENTS WITH ≥ 1 REPORTED STRESS LEAKS AT BASELINE
15 15 14 15 15 15 15 10 10 9 10 9 9 9
Per
cen
tag
e o
f P
atie
nts
Rep
ort
ing
0 o
r 1
Str
ess
Lea
ks
HIGH DOSELOW DOSE
B to 18 Mp=0.17 (NS)
B to 18 Mp<0.01
The percentage of high dose patients reporting 0 or 1 stress leak significantly increased from B to 18 M.
Percentage of Patients Reporting Satisfaction
DOUBLE-INJECTION PATIENTS WITH ≥ 1 REPORTED STRESS LEAKS AT BASELINE
HIGH DOSELOW DOSE
Basel
ine
1 M
3 M
7 M
9 M
12 M
18 M
Basel
ine
1 M
3 M
7 M
9 M
12 M
18 M
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
1/15 0/10 3/8 4/9 4/9
Per
cent
age
of P
atie
nts
Who
Wer
e M
ostly
Sat
isfie
d, P
leas
ed,
or D
elig
hted
The percentage of high dose patients reporting satisfaction significantly increased.
B to 18 Mp=0.03
B to 18 Mp=0.17 (NS)
2/15 4/15 4/15 6/15 4/15 5/15 4/10 0/10 4/10
Adverse Events After AMDC Injection
AMDCsn = 38
UTI (treatment-related) 5.3% (n = 2)
Acute urinary retention < 7 days (self-limiting) 5.3% (n = 2)
Hematoma at biopsy site 7.9% (n = 3)
Outlet obstruction 0%
Hematuria (visible blood in urine) 0%
Dysuria or increased frequency 5.3% (n=2)
Erosion; excreted or exposed material 0%
Pain at injection site 10.5% (n=4)
Urinary retention > 7 days, unspecified 0%
TAP cGMPCompacTAutomated Cell Culturing
Greater reproducibility
More efficiency
Easy to schedule operations
TAP cGMPCompacTAutomated Cell Culturing
Less variation Lot-to-Lot
Increased production
Less risk of operator contamination
Fewer consumables
Safety and Potential Effectiveness of Cook MyoSite Autologous Muscle Derived Cells for Treatment of
Stress Urinary Incontinence: 12-Month Results from a Dose Escalation Study
Kenneth Peters1, Larry Sirls1
Melissa Fischer1, Michael B Chancellor1
Melissa Kaufman2, Roger Dmochowski2, Daniel Biller2, Leslie Carr3, Sender Herschorn3
1. Beaumont Health System
2. Vanderbilt University Medical Center
3. Sunnybrook Health Sciences Centre
Baseline Characteristics
All patients had failed prior SUI treatment, including: Behavioral therapy (85.9%), Pharmacological therapy (32.8%), Surgical therapy (20.3%), and/or bulking agent injection (6.3%)
64 women received intrasphincter injection of either 10, 50, 100, or 200 million AMDC.
Primary outcome was safety
Secondary outcome was effectiveness
Clinical effectiveness was assessed in a subset of 48 patients with moderate to severe incontinence defined as greater than 3 leaks over 3 days and ≥ 3 g pad weight at baseline
1 lost to follow-up
4 Withdrew
Methods
No serious treatment related adverse events
Biopsy related event-all mild Hematoma 2/64 Bleeding requiring suture 1/64
Genitourinary within 30 days of injection Dysuria 3/64 Pelvic/abdominal pain: 3/64 Vaginal or urethral itching: 3/64 Hematuria: 2/64 Increased Frequency and Urgency: 1/64 Sensation of foreign object in urethra: 1/64
Safety
Conclusions Phase 2 trials completed
Phase 3 prospective multicenter double blind randomized trial started
First male SUI FDA compassionate IND trial started at Beaumont
Consideration of aging underactive bladder FDA compassionate IND trial
Study CentersSunnybrook Health Science Center
Department of Urology; Toronto, ON, Canada
Lesley K. Carr Sender Herschorn Ljiljana Petkovic Divina Buencamino Matty Mehrabi
University of Calgary, Foothills Medical Center, Department of Obstetrics & Gynecology, Calgary, AB, Canada
Colin Birch Magnus Murphy LorelDederer Magali Robert Sue Ross
William Beaumont Hospital, Dept. of Urology, Royal Oak, MI
Kenneth Peters Larry Sirls II Melissa Fisher Deborah Hasenau Michael Chancellor
Vanderbilt University, Department of Urology, Nashville, TN
Roger Dmochowski Melissa Kaufman PriyaPadmanabhan Harriette M. Scarpero Daniel H Biller Renee M. Ward