DREAM
Downstream Regulatory Element Antagonistic Modulator (DREAM) is a key molecule for pain regulation: Penninger and his group have shown in knock-out mice that loss of DREAM results in overproduction of prodynorphin which then inhibits pain without any apparent side effects. Thus, DREAM is an essential factor that controls the synthesis of the endogenous opioid dynorphin and therefore represents a new target for the treatment of pain. Importantly, loss of DREAM affected all modalities of pain ranging from acute chemical, heat, or mechanical pain to internal, inflammatory, and chronic neuropathic pain, indicating that DREAM is a master regulator of pain perception acting in neurons of the spinal cord.
 
Therapeutic approach
The functions of DREAM can be used for screening assays in a high-throughput format to identify compounds from huge substance libraries that release DREAM from the respective DNA, thereby activating the synthesis of the endogenous opioid prodynorphin. In essence, such compounds are not analgesics per se, but trigger the production of endogenous opioids in the treated individual. They represent a completely novel class of analgesics.
 
This project is performed together with Evotec AG (Germany) as strategic partner. A high throughput screening based on a biochemical assay has been performed successfully and led to several confirmed hits.