Periodic Reporting for period 1 - MEXOM (Development and characterization of extracellular vesicles an innovative cell-free therapeutical product for treatment of stroke)
Reporting period: 2018-09-03 to 2020-09-02
Stroke is serious life-threatening but unmet medical condition. It is the second leading cause of long-term disability in Europe and is the sixth leading cause worldwide. In the EU, the annual economic cost of stroke is an estimated €27 billion. Current stroke therapy is mainly based on general care and rehabilitation. 10-35% of stroke patients in Europe die within 28-30 days. Most strokes are caused by brain ischemia when blood vessel gets blocked, brain cells because of lack of oxygen get damaged and die. Microglia, brain immune cells, are the key cells initiating neuroinflammation in the injured brain area that evolves into amplifying brain inflammatory responses eventually leading to the secondary much worse brain damage.
Mesenchymal stromal cells (MSCs) are specific cells found in human umbilical cord that is usually discarded as medical waste. The cord tissues for this project were obtained from the 'Biobank Antwerpen' in Belgium, provided by the donors upon written informed consent. These cells can be isolated in the laboratory and secrete so called extracellular vesicles (MSC-EVs). The latter are very small, nano size biological particles containing many different types of therapeutically active molecules. During the last years, accumulating evidence show that MSC-EVs can stop brain inflammation and, on the top of that, start regeneration of already occurred brain damage in animal models. However, most of these studies produced MSC-EVs not according to the strict Good Manufacturing Practice (GMP) requirements applicable for medicinal drugs which is a must to be used on humans.
The Host of the project is Exo Biologics company located in Belgium, which is one of the pioneers in EVs field. The company has developed a proprietary and unique, fully GMP-compliant MSC-EVs production platform. Based on the mentioned state-of-the-art knowledge and unmet medical needs, MEXOM project's key aim was to develop and characterize at the Host’s laboratories an innovative MSC-EVs therapeutical product for treatment of stroke.
The key objectives of MEXOM project were successfully achieved. Firstly, a novel early-stage MSC-EVs drug candidate for stroke was developed, and its features were described. Secondly, its strong potential to inhibit brain inflammation was demonstrated in the laboratory. Eventually, a hypothesis how this drug works in stroke was formulated.
Mesenchymal stromal cells (MSCs) are specific cells found in human umbilical cord that is usually discarded as medical waste. The cord tissues for this project were obtained from the 'Biobank Antwerpen' in Belgium, provided by the donors upon written informed consent. These cells can be isolated in the laboratory and secrete so called extracellular vesicles (MSC-EVs). The latter are very small, nano size biological particles containing many different types of therapeutically active molecules. During the last years, accumulating evidence show that MSC-EVs can stop brain inflammation and, on the top of that, start regeneration of already occurred brain damage in animal models. However, most of these studies produced MSC-EVs not according to the strict Good Manufacturing Practice (GMP) requirements applicable for medicinal drugs which is a must to be used on humans.
The Host of the project is Exo Biologics company located in Belgium, which is one of the pioneers in EVs field. The company has developed a proprietary and unique, fully GMP-compliant MSC-EVs production platform. Based on the mentioned state-of-the-art knowledge and unmet medical needs, MEXOM project's key aim was to develop and characterize at the Host’s laboratories an innovative MSC-EVs therapeutical product for treatment of stroke.
The key objectives of MEXOM project were successfully achieved. Firstly, a novel early-stage MSC-EVs drug candidate for stroke was developed, and its features were described. Secondly, its strong potential to inhibit brain inflammation was demonstrated in the laboratory. Eventually, a hypothesis how this drug works in stroke was formulated.
During the MEXOM project, the Researcher Gabrielis Kundrotas co-founded Exo Biologics and was employed as Head of Research & Development department. He started a new laboratory and developed a small version of GMP-compliant production platform. By using it, he developed and characterized 2 versions of novel MSC-EVs drug candidates for stroke treatment. Then, he tested the EVs in co-culture with mouse microglia primary cells and showed that both versions inhibit neuroinflammation very strongly and with a fast effect which would be required for effective stroke treatment. Researcher identified specific small molecules, called microRNAs, that might be, at least partially, responsible for this therapeutic effect. He hypothesized that part of these small molecules is protected inside the EVs that enter brain immune cells and stop them stimulating inflammation, thus potentially blocking further brain damage.
During MEXOM project the Researcher, along with the Supervisor, brought together a wonderful research and development team consisting of both local colleagues and external partners that together developed this innovative drug.
The Researcher identified a list of patentable innovations during this project. Exo Biologics expects to evaluate these innovations and to submit patent application in 2022, after which the selected results will be shared with the scientific and broader public.
During MEXOM project the Researcher, along with the Supervisor, brought together a wonderful research and development team consisting of both local colleagues and external partners that together developed this innovative drug.
The Researcher identified a list of patentable innovations during this project. Exo Biologics expects to evaluate these innovations and to submit patent application in 2022, after which the selected results will be shared with the scientific and broader public.
By being one of the pioneers in the EVs field, Exo Biologics is addressing regenerative medicine industry demands. MEXOM project was fully integrated into the Host EVs production and quality control system, therefore introduced the first drug candidate in the company’s pipeline in the field of neurology. Very promising project’s results encourage the company to develop further after MEXOM this innovative drug.
The results generated during MEXOM project have already served other scientific projects at Exo Biologics by supporting the development of more advanced MSC-EVs drugs towards clinical application in the fields of pulmonology and gastroenterology. New procedures were developed and applied at the Host for the characterization of EVs drugs, thus providing additional information requested by the Regulatory Authorities. The efficient, reproducible, and cost-effective small scale EVs production platform is being used in the intense studies aimed at determining the molecular mechanisms of MSC-EVs drugs in specific bowel and lung diseases.
In summary, results of MEXOM project accelerated the development of several EVs drugs towards clinical application where they have been long awaited by millions of intestines, lung, and brain patients.
The results generated during MEXOM project have already served other scientific projects at Exo Biologics by supporting the development of more advanced MSC-EVs drugs towards clinical application in the fields of pulmonology and gastroenterology. New procedures were developed and applied at the Host for the characterization of EVs drugs, thus providing additional information requested by the Regulatory Authorities. The efficient, reproducible, and cost-effective small scale EVs production platform is being used in the intense studies aimed at determining the molecular mechanisms of MSC-EVs drugs in specific bowel and lung diseases.
In summary, results of MEXOM project accelerated the development of several EVs drugs towards clinical application where they have been long awaited by millions of intestines, lung, and brain patients.