Why is basic research being carried out

How can the link between basic research and drug development be improved?

Academic research plays a key role in identifying targets against which a new drug should be directed - including understanding the role of the target in the development or progression of the disease to be treated. As an important next step in drug development, the results from preclinical basic research must be transferred to clinical research (English: "translation"), which is usually carried out by the pharmaceutical industry.

But how does basic research know which steps are necessary to ensure industrial connectivity? How should resources best be allocated to prioritize key activities and identify potential issues during drug development as quickly as possible? And which quality requirements need to be taken into account in order to increase the chances of success?

In order to answer these questions, the Federal Ministry of Education and Research (BMBF) initiated the funding measure “Target validation for the development of pharmaceutical active ingredients” in 2017. In this context, projects from preclinical research are supported in order to experimentally confirm (validate) new molecules as targets for potential drug candidates and thus create a solid basis for further drug development.

In addition, with GOT-IT (the abbreviation stands for "Guidelines On Target assessment for I.nnovative Therapeutics ") sponsored an accompanying project. The aim of the project was to create a guideline that describes the decisive criteria for successful target validation and target evaluation and supports scientists in identifying and prioritizing activities for the critical evaluation of new targets. Scientists from the Berlin Institute of Health (BIH) and the Charité - Universitätsmedizin Berlin (Prof. Ulrich Dirnagl), as well as the Fraunhofer Institute for Molecular Biology and Applied Ecology IME in Frankfurt am Main (Prof. Michael Parnham) and PAASP GmbH were involved in this project in Heidelberg (Dr. Christoph Emmerich) involved.

In order to ensure the comprehensibility and feasibility of the GOT-IT guidelines, experience was obtained from project managers and mentors of the BMBF target validation projects as well as from experts from industry, technology transfer offices and academic institutions during its development.

The guide was now in the magazine Nature Reviews Drug Discovery released.

The GOT-IT concept of the critical path

In order to take into account the requirements of different diseases as well as the different availability of resources, the GOT-IT recommendations were built on a modular system, which enables an appropriate and flexible adaptation to project-specific needs. So 5 'building blocks' were defined, which summarize the decisive aspects of target validation and target evaluation:

  1. Causal link between target and disease (is the target molecule really decisive for the course of the disease?);
  2. Safety (can the target be changed without it becoming dangerous for the patient?);
  3. Medical and commercial needs and legal requirements;
  4. Technical feasibility of a planned project;
  5. Important aspects for the development of active substances against non-human target molecules such as bacterial or viral targets.

With a set of 40 key questions, the GOT-IT recommendations also offer the possibility of selecting relevant modules and module-related activities for a planned project and arranging them in a specific critical path. This critical path represents the optimal path between a starting point (e.g. the identification of a new target) and the project goals (e.g. the initiation of clinical tests on patients).

As a further important point, recommendations were included in the guideline that deal with the robustness and reproducibility of the data obtained in order to increase confidence in the results and to support critical decisions along the critical path.

In summary, the GOT-IT guideline gives scientists, editors of scientific journals, funding organizations and donors recommendations to validate and check basic knowledge of new targets according to industrial standards. The guidelines can support funding organizations and donors in identifying high-quality projects. This lays a strong basis for the subsequent drug development so that translational research can be designed more effectively and more target-oriented in the future.