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Multisystem Cell Therapy for Improvement of Urinary Continence

Periodic Reporting for period 2 - MUSIC (Multisystem Cell Therapy for Improvement of Urinary Continence)

Reporting period: 2018-07-01 to 2019-12-31

"Stress Urinary Incontinence (SUI), which is defined as the unintentional loss of urine, affects over 200 million people worldwide. This condition has a prevalence of 20-50% in women, thereby creating an immense socio-economic burden. The currently available treatment strategies entail various complications and offer only short-term relief to the patients. Regenerative medicine (RM) and tissue engineering (TE) using the patient’s own cells for transplantation (autologous transplantation) offers a feasible alternative for functional restoration of a damaged urinary sphincter muscle and represents an ideal treatment option, that could reverse the underlying pathological conditions. To this aim, we initiated the project entitled “Multisystem cell therapy for improvement of urinary continence” – MUSIC.
The main aim of the MUSIC consortium is to translate basic knowledge on cellular therapies and RM into the clinic by undertaking a ""first-in-man"" multisystem study using autologous muscle precursor cells (MPCs) in a combination with neuromuscular electromagnetic stimulation (NMES) in 40 female patients. Throughout the project’s lifetime, we will specifically address safety and efficacy of the proposed novel treatment, as well as reproducibility of the therapeutic effect. Further objectives are the optimization of the advanced-therapy medicinal product (ATMP) towards a manufacturing procedure that is totally free of animal-derived components (xeno-free) and that is facilitated by using a bioreactor. Furthermore, the introduction of a novel injection technique will allow for a more efficient and precise implantation of the final product.
The MUSIC consortium features a unique infrastructure, combining expertise in the fields of RM, urology, cellular biology and biomaterials throughout Europe (CH, NL, UK, A, D). We have an exclusive opportunity to determine the validity of this MPC cellular treatment in combination with NMES and to further develop its practicability and clinical efficacy. Our ultimate goal is to significantly improve the patients’ quality of life and to exploit future commercial opportunities by spreading the know-how to various smaller RM centers and companies within Europe and beyond, thus, making personalized medicine using autologous cells a realistic SUI treatment option.
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From the beginning of the project, we pursued the main milestones to achieve the successful translation of the know-how into the clinical setting. We accomplished various pre-clinical tests and re-submitted all required documents to the authorities to assure the highest quality and safety of the cellular product. The surgical team of the MUSIC project performed high-precision test-injections in cadaver, using a novel ultrasound-guidance tool. We successfully completed the GMP validation and verification procedures and could enroll our first patient.
Due to a fruitful collaboration and successful transfer of know-how within the consortium, we managed to kick-start the development of further objectives of the MUSIC project. The advances in the set-up of a totally xeno-free cell culturing procedure are promising. Fine-tuning for the production settings is currently ongoing. Moreover, the transfer of our current culturing system into a bioreactor-automated setting was successful, allowing a highly efficient cell expansion. Furthermore, with combined efforts, we are developing two injection techniques/tools in parallel, the prototypes of which are already available for pre-clinical testing, in order to optimise the settings for precise and efficient implantation of the final product prior to introduction into a clinical setting.
The next development steps of our project would launch the specific settings for the completely xeno-free, scaled-up cell production and minimally-to-non-invasive implantation possibilities, allowing for a wide-spread application of the therapy in numerous patients within Europe and beyond in the next phases of the study. Succeeding in this will offer a time- and cost- efficient solution for tangible functional muscle regeneration, thereby significantly increasing the quality of life of SUI patients. With a constantly aging population, the market potential for cellular therapies is growing daily. We therefore believe that the exploitation possibilities of the MUSIC outcomes will be of great importance and already have great potential to be life-changing.
The new procedure to treat SUI will result in a long- lasting relief for patients with minimal risk of complications. An important goal for the consortium is to develop a procedure that is safe, affordable and minimally invasive for the patients. To optimize the safety of the new cell-based product, we aim to have a production process that is completely free of animal-derived components. Two of our consortium partners are developing components that are either synthetic or human-derived. In addition, to ensure that the new procedure remains affordable, we are also working towards a more efficient way to grow the cells. Automation of the cell culture process will reduce production cost and thereby the overall costs for the therapy, making it reasonably priced for the general patient population. Finally, to minimize patient discomfort, we are optimizing the application method to make it minimally invasive. The developments can be used in other areas as well, so that the impact of the results of this project go beyond the application in SUI. As a result, the MUSIC project will provide a superior treatment for thousands of women (and later on men) with SUI, while the developed technologies will benefit the wider field of cell-based therapies.
Mulitsystem Cell Therapy for Improvement of Urinary Continence