Brain conditions, including brain tumors and neurodegenerative diseases such as ALS and Alzheimer's, Parkinson's and Huntington's disease, have a major impact on patients, their loved ones and society as a whole. The treatment of these conditions is often very drastic, and in the case of neurodegenerative diseases, options are mainly limited to symptom management, as no cure currently exists. When developing drugs for neurological diseases, one of the challenges that must be overcome is the blood-brain barrier. This highly-selective barrier consists of unique cells lining the tiny blood vessels in the brain and acts like a protective filter, preventing harmful substances in the blood from entering the brain. In almost all cases, drugs are also prevented from reaching the brain, which makes the effective treatment of neurological diseases all the more difficult.
Microbubbles and focused ultrasound
This creates a need for a method to temporarily open the blood-brain barrier in order to more effectively deliver drugs to the brain. A solution lies in the use of microbubbles, combined with focused ultrasound. These microbubbles, approximately 100 times smaller than a human hair, are injected directly into the bloodstream. Once they reach the blood vessels in the brain, they are activated locally by focused ultrasound and start to vibrate. This temporarily opens the blood-brain barrier, allowing drugs to reach the targeted areas of the brain more effectively.
Controlled and safe
Initial clinical studies with existing microbubbles have already demonstrated that this technique is viable and safe for patients with a brain tumor or neurodegenerative condition. The next step is to study clinical outcomes and the impact on patients’ life expectancy. While methods to administer microbubbles already exist, there is a need for standardized and controlled delivery, says Peter Frinking, managing director and chief scientific officer at Curix. The company is developing a prototype injector system that creates new microbubbles and injects these intravenously in a controlled manner. “Our system is unique and produces microbubbles that all react the same to focused ultrasound. Their behavior is therefore more predictable, enabling controlled and safe drug delivery. This first prototype microbubble injector system has already been tested successfully in a laboratory environment.”
Pediatric oncology
In pediatric oncology, this technology can pave the way for improved treatments for children with brain cancer. This is the second most common form of childhood cancer after leukemia. Every year, around 120 children in the Netherlands are diagnosed with brain cancer. Some forms, such as brainstem cancer, have a very low survival rate. In 2023, Curix therefore joined the collaborative project FUMES together with the research group of Dannis van Vuurden, pediatric oncologist at the Princess Máxima Center for pediatric oncology. Frinking: “Our technology is used at the Princess Máxima Center for pre-clinical studies on the use of focused ultrasound for the treatment of brainstem cancer in children. This project is made possible with the help of Stichting Kinderen Kankervrij (KiKa) through a grant from Health~Holland. Together with our sister company Sync Biosystems, which is also part of the Demcon Group, we are exploring how the right drugs for cancer treatment can be absorbed more effectively by the brain after temporarily modulating the blood-brain barrier.”
Animal-free
At the European level, Curix is collaborating with various partners on the grant project UNLOOC. This project is intended to demonstrate how organ-on-chip technology can contribute to the development of improved therapies without the use of animal testing. For this project, a special version of the injector system is connected to an organ-on-a-chip model of the blood-brain barrier. Frinking: “This allows us to test our technology and optimize drug delivery protocols, all without using animals. It also helps to expedite the development of new drugs for brain diseases.”
Participation
The next step after the laboratory research will be to test the technology in patients. Curix is now further developing its prototype to a injector system suitable for initial clinical studies. “The participation of Twinning Participaties, which supports innovative digital technology initiatives in Eastern Netherlands, allows us to take the next step in the development of our technology”, says Frinking. “Ultimately, we hope that our system can be used for the improved and early treatment of brain diseases, in some cases even before clinical symptoms appear, such as with Alzheimer's disease.”
Clinical application
For the development of this technology, Curix is supported by Demcon life sciences & health. “Demcon has all the expertise required for the development of clinically applicable medical systems”, says Michiel Jannink, vice president of Demcon life sciences & health. “We tackle technological challenges in order to create solutions for societal problems. To that end, we collaborate extensively with research institutions and businesses. The participation of Twinning Participaties allows us to get Curix’s microbubble injector system ready for clinical evaluation.”
Major social impact
Curix offers a prime example of the type of digital innovation that Twinning Participaties seeks to invest in, says director Jaap Spoorenberg. “Curix's technology has clear clinical relevance, with the potential to make drugs for brain diseases far more effective. With this technology, Curix has major social impact and generates valuable scientific knowledge, which researchers and pharmaceutical companies can also benefit from. In this way, Curix boosts the innovation power of the Netherlands.”
About Demcon
Demcon (1,100+ employees) develops, produces and delivers technology and innovative products. The Demcon Group has locations in Best, Delft, Enschede, Groningen, Leiden, Maastricht, Scheveningen, Münster (Germany), San José (US), Singapore, and Tokyo (Japan). The company was founded out of its founders’ passion for combining creativity and technical skills to solve complex technological and social issues. On top of that, Demcon is committed to fostering entrepreneurship and investing in talent and education.
About Twinning Participaties
Twinning Participaties emerged from Stichting TReNT, which constructed a fiberglass network in the Eastern Netherlands over a period of twenty years. Twinning Participaties uses the funds from the network's sale in 2020 to network operator Alliander to invest in innovative digital technology initiatives in the provinces of Gelderland and Overijssel.