Entwicklung eines systematischen Verfahrens zur Untersuchung von indikationsübergreifenden Signalwegen und Zielmolekülen für pharmazeutische Forschung und Entwicklung

Drugs that can be used to treat more than one disease are not only a great benefit for patients but have also proven to be an economical advantage for developing pharmaceutical companies. Although a great deal of information is available about signaling pathways and functional relationships between drug targets, so far the development of these cross-indication drugs has been mostly a product of chance. The goal of this work was to establish a systematic methodology for identifying drug targets and signaling pathways that are common in more than one disease (common targets/common pathways). An Access-based database was built that automatically and systematically analyzes connections of therapeutic areas and indication groups via common targets and pathways. An adjacent prioritization allows naming drug targets that have an increased chance to be important in more than one indication. The database allows identifying both direct connections between therapeutic areas via common targets as well as indirect connections via common signaling pathways that do not share common targets. In brief, it is possible to analyze the following: 1. Connections of therapeutic areas via common pathways Shared biological pathways interconnect different therapeutic areas. The degree of their connectivity can be visualized in a matrix. Depending on the focus of the analysis it is possible to weigh the connections according to their biological or commercial strength. 2. Connections between indication groups via common pathways Most pharmaceutical companies already have established research focus areas. The database therefore enables the identification of the closest connections of indication groups within two predefined therapeutic areas. These indication groups have the highest chance to be targetable by cross-indication projects. 3. Identification and prioritization of common pathways Using the database it is possible to identify the pathways that are most important for the connection of two indication groups. This knowledge supports specialization of research tools and capabilities along those pathways that are most likely to encompass common targets and common physiological functions. 4. Identification of common target candidates For a strategic focus on indication groups and pathways, it is possible to create a list of both known common targets as well as novel common target candidates. Known common targets are already in research and development for both of the selected indication groups. Common target candidates are part of the common pathway, however have only been pharmaceutically addressed for one of the indication groups. Due to their role in the common pathway, these targets have an increased likelihood to be of use for both indication groups in the future. 5. Prioritization of common target candidates Common target candidates can be evaluated in four categories: “biological evidence of a cross-indication function”, “feasibility of drug development”, “competitive environment” and “strategic fit”. This allows the separation of more promising candidates from less optimal ones. Pharmaceutical companies and academic research groups could use this novel methodology to systematically support research and development of common targets and pathways. To ultimately succeed with the development of cross-indication drugs, intensive communication and cooperation across therapeutic areas are most critical.