- Climate, Environment & Health
FASTER DEVELOPMENT OF EFFECTIVE MEDICATIONS
The Covid 19 pandemic has send a signal to large segments of society what people with rare diseases have long known: Providing the world's population with targeted medicines and rapidly developing new compounds poses major challenges for the pharmaceutical industry.
A rapidly evolving new disease often has profound societal consequences. The need for methods to develop and deliver safe and efficient compounds to patients in a set time frame at an acceptable cost is enormous. It is not unusual for a single drug to take up to 20 years of development and cost several billion euros before it is approved. As a result, the fewer people who need the drug, the less pharmaceutical companies can cover their development costs through the mass market. From the patient's point of view: The lower the development costs, the more likely I am to get the right drug for my rare disease.
Recovery is the motivation for Ph. D. Maximilian Benz. The main research topic in the context of his doctoral thesis at KIT: chemBIOS, a promising on-chip platform that is supposed to enable rapid drug development. The focus of his research is the miniaturized and parallelized development of active ingredients in the early phase of drug development. Until now, chemical synthesis of active ingredients and screening for biological efficacy have been incompatible due to different basic conditions and have proceeded in separate, repetitive steps. With the help of the chemBIOS platform, this is to be improved and, above all, accelerated by linking the chemical part with the biological part and placing them on a common surface.
"What makes our research unique from others is the miniaturized and parallelized chemical synthesis in liquid phase. What is well developed so far is the solid-phase synthesis," says Ph. D. Benz. In solid-phase synthesis, compounds are firmly anchored to the surface, allowing them to be modified and changed as they progress. This allows the production of important biomolecules such as DNA, peptides or even sugars. In addition, however, there are many more classes of biologically active substances for whose production solid-phase synthesis is unsuitable. "With the chemBIOS platform, we can produce these compounds in liquid phase. It offers us a very wide range of organic chemistry methods. We can produce a wide variety of chemical compounds and also study them directly in a biologically way. This advantage compared to other chip developments is a unique selling point with great potential," reports Ph. D. Benz proudly.
The chemBIOS platform is a glass slide whose surface is chemically modified to place thousands of nanodroplets on it. Each individual droplet functions like a very small vessel that carries out chemical reactions or even biological investigations. The operating principle of the chip corresponds to the conventional procedure, but in a highly miniaturized and parallelized form. In the first step, chemical substances are printed onto the chip as droplets, where they react with each other to form new compounds. The compounds can then be analyzed directly on the chip, for example by mass spectrometry or various types of spectroscopy. Cell experiments are also possible to test the biological activity and determine which of the compounds are candidates for further drug development.
In an initial proof-of-principle study of Ph. D. Benz's and the group's platform, published in the journal Nature Communications, 75 compounds could be prepared, analyzed and biologically tested simultaneously in just three days, requiring a total of only one milliliter of reagents and solutions. Classically, the entire process takes several weeks and requires several liters of solutions. "The potential is much higher. In further tests, I generated such a surface with much smaller spots and droplets" explains Ph. D. Benz. This way, the process does not only increas throughput and saves a lot of time and effort, but also reduces the amount of chemicals, cells and other consumables used. The entire phase of early drug development is rapidly accelerated and made more efficient with the help of the chemBIOS platform. This is a ray of hope for people with rare or new diseases that have not been adequately researched yet and for which no suitable drug exists until now.
The platform is being commercialized by Aquarray, a spin-off from KIT, and is supported by the European Union's Horizon 2020 research and innovation funding program. "We are already working with industry and are looking for more collaboration partners to further develop the platform. We are very grateful for the feedback from the industry. It helps to tell, which changes still need to be made so that our technology can be used on a broad scale," Ph. D. Benz tells us with a glimpse into the future.
"My personal motivation is to help sick people. I want to make the drug development process faster and more cost-effective. Money should not be the deciding factor in whether a drug is developed or not. The patient has to be the main reason."
- Institute of Biological and Chemical Systems - Functional Molecular Systems (IBCS-FMS)
- Turbo chip for drug development
- Aquarray Website
Images: Magali Hauser / KIT