Cells from skeletal muscle fibres, as shown above in a SEM image, are the basis of an autologous cell therapy platform developed by Cook MyoSite.Credit: Steve Schmeissner/SPL/Getty Images
Muscle-related damage and deficiencies impact a patient’s quality of life, and treatments can be limited or non-existent. Some patients find relief in physical therapy or surgery, but such approaches often do not address the underlying cause of damage. Cook MyoSite has developed a cell-therapy platform that uses striated muscle progenitor cells to augment weakened or damaged muscles that cause certain conditions that are hard to treat. Ron Jankowski, Ph.D., the Vice President of Scientific Affairs at Cook MyoSite, discusses issues surrounding muscle-related disorder research, and the potential of cell therapy.
Ron Jankowski, Ph.D., the Vice President of Scientific Affairs at Cook MyoSite.Credit: Cook MyoSite
We are building a cell therapy manufacturing and delivery platform that can potentially support a number of clinical conditions. Our platform is an autologous muscle-derived cell therapy, meaning we use a patient’s own tissue. In the absence of concomitant gene therapy, muscle progenitor cell therapy is most applicable for functional augmentation and strengthening of smaller muscles, such as sphincter muscles.
How does muscle progenitor cell therapy work?
Cell therapy using striated muscle progenitor cells is hypothesized to work the same way the body’s normal muscle regeneration process does. Progenitor cells reside on the periphery of muscle fibres, and are quiescent in undamaged muscle. But in response to tissue injury or stresses, they proliferate and fuse with existing muscle fibres. They also differentiate to form new muscle fibres which integrate with the existing vasculature and nerve supply. Nonclinical studies demonstrate that when progenitor cells are removed from one muscle in the body and are implanted into a weakened or deficient one, they engraft into the injected muscle and improve strength and function.
We take a small biopsy from the patient’s thigh, about 150 mg of muscle tissue. We then isolate and purify these cells, expand them in culture, and concentrate them into a cryopreserved injectable formulation. We can receive samples from, and ship final products to, any location.
How does this approach relate to the larger field of muscle-related disorder research?
A lot of clinical work was performed in the 1980s and ‘90s, for muscular dystrophies, but much of it was determined to be ineffective. This was largely due to the scale of disease owing to genetic mutation, where all muscles of the body are affected. In contrast, we target muscle-related conditions where a small augmentation could have a big benefit.
One such area involves weakened sphincter muscles. For instance, we are researching female stress urinary incontinence, which is involuntary leakage of urine during physical exertion. It’s a serious enough condition that some women seek aggressive, invasive procedures to relieve their symptoms. We also are currently pursuing and supporting clinical trials for fecal incontinence, tongue dysphagia, and underactive bladder.
While the muscle disorders we work with are not life-threatening, they are serious conditions and can have a substantial impact on quality of life. Patients afflicted with these conditions often start therapy with noninvasive approaches like physical therapy, to attempt to retrain and strengthen muscles. If they don’t see a benefit, and if the symptoms are severe enough, they move on to more invasive surgical approaches. Those treatments, which can involve whole autologous tissue transfer or permanent implantation of a synthetic material, can provide benefit, but they also are associated with increased risk.
Which therapies have gone through clinical trials?
We have performed investigative trials for more confined, focal muscle conditions such as stress urinary incontinence and fecal incontinence. For female stress urinary incontinence, two phase III randomized controlled clinical trials are ongoing in the United States and Europe. We’re planning a third in Japan. There is also an ongoing fecal incontinence trial in Canada and Europe.
We’re providing manufacturing support for a physician-sponsored investigational tongue dysphagia study being conducted in the U.S. We’ve also previously provided similar support for a physician-sponsored trial in the U.S. to investigate treatment for patients with underactive bladder, which is a weakened bladder with very limited or no voiding ability. You can find a full list of our clinical trials on Clinicaltrials.gov.
What role do partnerships play in your work?
We are in a unique position in that we have facilities infrastructure in manufacturing and testing, as well as the regulatory expertise in this emerging industry. If clinicians and researchers think our muscle progenitor cell therapy platform could help with the development of therapies, we have multiple ways to potentially support their research.
The ongoing investigational trial on tongue dysphagia was initiated by a physician who approached us after successfully completing pre-clinical research. The physician had established feasibility and wanted to pursue a small clinical trial to see if our platform could be a possible therapeutic option for these patients.
That’s just one example of a research partnership that pairs our manufacturing and capabilities with their clinical knowledge to pursue improved patient care. We welcome many more.