The marketing of a clinical study

At the Department of Urology of the University Hospital Zurich, a therapy against urinary incontinence is currently developed, in which adult muscle precursor cells are implanted – this EU project involves institutes from five different countries. The project hub is the Laboratory for Stem Cell Therapy and Tissue Engineering. Paying a visit to project leader Deana Mohr-Haralampieva, DSc, and her team.

She made it. Despite the by now eight months of ongoing corona crisis and all the restrictions that resulted from it, Deana Mohr-Haralampieva, the Clinical Project Manager and Coordinator of the EU project with the resounding name MUS.I.C, succeeded in founding a spin-off at the end of October. The company with the equally resounding name MUVON Therapeutics AG shall one day transfer the therapy developed in the laboratory into practice. Today, Deana Mohr (how the thirty-four-year-old of Bulgarian descent simply calls herself) sits in her office at the Laboratory for Stem Cell Therapy and Tissue Engineering in Schlieren and is visibly happy: «Indeed, corona was not part of the risk mitigation plan for MUS.I.C.» Yet still, so far everything has worked out.

The therapy is called Multisystem Cell Therapy for Improvement of Urinary Continence and aims to help patients with stress urinary incontinence. Estimates suggest that in Switzerland alone, approximately 400,000 people suffer from it; globally, there are even 200 million. Most of the patients are women whose bladder muscles are weakened by births, surgeries or age-related degeneration. However, men may equally be affected, especially those who had to undergo a prostate operation. Common to both groups is the fact that the quality of their lives is massively impaired and their physical activity is restricted.

«Corona was not part of
the risk mitigation plan
for MUS.I.C.»
Deana Mohr-Haralampieva

The currently available treatments counteract the symptoms, for example by means of physiotherapy or by surgically inserting synthetic slings. The new therapy, however, approaches the very root of the problem: the physicians obtain a small biopsy from the patient, from which the research team isolates and expands the adult muscle precursor cells under most vigorous clean room conditions in the laboratory. Thereafter, the cells are injected into the bladder-closing muscle of the patient where they help to regenerate the closing muscle. There are many great advantages of this kind of treatment: the body basically regenerates itself. Additionally, as the stem cells are the treated adult’s own, there is no need addressing ethical problems as seen with stem cells from embryos or other donors. Also, unlike possible for major surgical procedures, the risk of complications can be ruled out, just as the potential side effects of medication therapies. What is more, there is no risk of the body rejecting the implant as the tissue has grown from autologous cells.

A project planned well in advance

The origins of this project date from 2008 when Professor Daniel Eberli, MD, PhD founded the Laboratory for Stem Cell Therapy and Tissue Engineering at the Department of Urology. During the several years of his research stay in the United States, he had gained valuable experience in the field and had realised the great potential of this kind of regenerative medicine for the field of urology as well. In 2012, the cell and molecular biologist Deana Mohr-Haralampieva joined in. With her doctoral thesis about a joint SNSF project of the University of Zurich and ETH Zurich as well as the Biozentrum of the University of Basel she was able to prove the safety and efficacy of muscle precursor cell tissue transplantation in animals: the isolated cells successfully form muscle fibers and also remain where they were implanted. Shortly before the doctoral degree defense, Swissmedic approved in 2015 that the therapy could be further developed on humans, subject to certain obligations. This was the birth of the MUS.I.C. Project and Deana Mohr-Haralampieva did not only stick with the project, she also proceeded with a further education in clinical trial management in order to ideally accompany the process.

Political problems

The aim was, from the very beginning, to apply for EU research funding. Research involving human subjects is very expensive and working with adult stem cells costs much more than with others. However, after the acceptance of the Swiss federal popular initiative «Against Mass Immigration», Switzerland was partially barred from the EU research programmes. Because of the uncertainty, the chances to receive EU funding for projects coordinated from Switzerland were reduced to a minimum. MUS.I.C. made it anyway: The proposal was submitted in April 2016; in August, the EU confirmed a contribution of six million Euro. «I was jumping for joy,» Mohr-Haralampieva recalls. This project was one of the very few Swiss coordinated projects to receive EU funding that year.

From the lab to the clean room to the clinic

By now, Switzerland is once again fully associated to the EU funding programme – and MUS.I.C. is at the stage of the first clinical trial. In January 2020, muscle tissue the size of half a sugar cube was obtained from the first patient’s lower leg. In the laboratory of the innovation centre Wyss Zurich, which provides the clean room for this project, the muscle precursor cells were extracted from the original tissue, expanded in the incubator and subsequently mixed with the carrier substance collagen.

The cell cultures are expanded for three to four weeks. The ideal number of cells is 80 million. Shortly before the nationwide lockdown in Switzerland, the cells were injected into the bladder-closing muscle of the first female patient. Subsequently, the muscle was supported by electromagnetic stimulation during six weeks. Until the end of November, seven of the patients designated for the first clinical phase will have been treated. Additional female patients are currently recruited: women interested in the study may sign up directly on the project’s website

«The maximum effect sets
in between three and six months
after the procedure.»
Florian Schmid

The project involves a total of 22 specialists in five European countries: Collagen Solutions in Glasgow, Scotland, develops and produces collagen components for use in regenerative medicine, medical devices and research. For the team of MUS.I.C., it developed and optimised a system for the manufacture of collagen from human fibroblast cells with hollow fibre cell cultures. What is more, the company collaborates with the University of Zurich on the development of a syringe that enables the blending of collagen and cells at the exact injection location.

The second partner is the Institute for Transfusion Medicine of the Paracelsus Medical University Salzburg. It specialises in the development and production of blood products and cell therapeutics. For MUS.I.C., it delivers the human platelet lysate, the so-called Pooled Human Platelet Lysate or pHPL. This substance consisting of blood platelets stimulates the reproduction of cells.

Scinus Cell Expansion B.V. in the Netherlands develops a bioreactor technology aimed to reduce the manufacturing costs of the still highly expensive cell therapy. The company provides the MUS.I.C. Project with an affordable protocol for the production and cultivation of the muscle precursor cells.

The Department of Urology of the University Hospital Tuebingen, in turn, offers MUS.I.C. its expertise in the treatment of stress urinary incontinence. The German research group develops a new technology that sprays the cells into the tissue instead of injecting them by means of a needle. This procedure aspires to enable improved distribution and a more precise dosage in the sphincter muscle.

The prospect of a lasting improvement

However, the bulk of the work is accomplished by the team in Zurich. There are Daniel Eberli and Deana Mohr-Haralampieva and seven other people who are fully dedicated to the project. Florian Schmid, a medical doctor working in the Department of Urology, joined the team in 2017. During the planning phase, he committed himself mainly to ethical issues and is responsible for the clinical part of the study, that means, he chooses the patients, treats them and cares for them afterwards in order to monitor the safety and feasibility of the medical procedure. «The maximum effect sets in between three and six months after the procedure,» he states. And how long will it last? Schmid cannot yet provide an exact time frame. Depending on the patient, he says, five years would already be very helpful. And of course, the goal is to achieve a lifelong cure.

Jenny Prange joined the team in 2017 as well. She is the Head of Good Manufacturing Practice (GMP) and responsible for the set-up and processing of the GMP-compliant production of muscle precursor cells. Already during the process validation phase, she developed with her GMP team mates all the relevant protocols, including those for testing an entire range of materials specified for the use in the clean room. Now, during the clinical phase, she is in charge of monitoring the working methods in the clean room. Prange earned her PhD in Integrative Molecular Medicine from the University of Zurich and further expanded her knowledge in stem cell research at Roche.

Two technical members of staff, a study coordinator, a gynaecologist and a business developer make the team complete. The latter, Steve Kappenthuler, is, like Jenny Prange, one of the co-founding members of Deana Mohr-Haralampieva’s spin-off MUVON Therapeutics AG.

A name indicating the way

MUVON is the acronym for muscle, volt and on from switch on, that is for the muscle that is activated by means of electromagnetic stimulation. At the same time, the name is a phonetic call to action: move on – move forward! The first objective of the company is to market the regenerative treatment of stress urinary incontinence. In the future, the plan is to expand the autologous transplantation, i.e. the transplantation of cells removed from the patient’s own body, to other skeletal muscles as well. What is Deana Mohr-Haralampieva’s personal motivation to dedicate herself to the cause on a daily basis and in the long run? She is fascinated by the fact that the project leads from bench to bedside, as the scientists say, that achievements made in the laboratory can be put directly into practice. And, she adds: «That autologous cells can become functioning tissue and thus cure illnesses.» Indeed, these are wonderful prospects.

Interview with Deana Mohr-Haralampieva (in German)
Deana Mohr-Haralampieva

Deana Mohr-Haralampieva is the Clinical Project Manager and Coordinator of the Horizon 2020 MUS.I.C. Project at the University of Zurich, a project that develops a regenerative treatment with autologous cells for the treatment of stress urinary incontinence. She leads a project team of experts from five European countries. In addition, she is the CEO of the start-up company MUVON Therapeutics AG, which was founded in October 2020 and aims to put the cell therapy on the market and develop it further in the future. Deana Mohr-Haralampieva obtained her MSc in Cellular and Molecular Biology from the University of Constance and earned her PhD at the Institute of Pharmaceutical Sciences at ETH Zurich and at the Laboratory for Tissue Engineering of Professor Daniel Eberli, MD, PhD. Her PhD thesis dealt with the safety and efficacy of human muscle precursor cell implantation in animals for studying functional muscle regeneration. The results of this thesis lead to the authorisation of the MUS.I.C. study for clinical translation and motivated her to proceed with a further education in clinical trial management. Deana Mohr-Haralampieva is married and mother of two young children.

Horizon 2020 Project

MUS.I.C.:  Multisystem Cell Therapy for Improvement of Urinary Continence

  • Programme: Collaborative project (5 partners)
  • Duration: 60 months
  • Contribution for University of Zurich: 4’260’357 €