Pain-causal Human Tissue TenZero’s technology is grounded in its unique, proprietary human tissue collection. Working under IRB-approved protocols, Dr. Falci has collected samples of electrically hyperactive, pain-causal dorsal root entry zone (DREZ) tissue and electrically normal control tissue (also referred to as “hot” and “cold,” respectively). More than 5,000 proteins have been measured in each tissue sample using the SomaScan 5K assay. For any given protein, the hot:cold ratio is a measure of how much more abundant the protein is in pain-causal vs. normal DREZ tissue.
The Red Box The data can be depicted in a volcano plot (see graph) in which each dot represents one of the measured proteins. Dots that lie further to the right represent proteins that have a higher hot:cold ratio: they are more abundant in electrically hyperactive DREZ samples and may be implicated in neuropathic pain processes. The y-dimension reflects statistical confidence (points that are higher are associated with lower false discovery rates). Critically, proteins of interest, such as those in the red box, are identified using pain-causal tissues from humans actually experiencing neuropathic pain rather than rodent models.
Human Pain Proteome Database™ TenZero is developing its proprietary Human Pain Proteome Database based on these proteomic data, integrating information about each measured protein: pathway associations, protein classifications (e.g., kinases, phosphorylases, signaling molecules, receptors), tractability for small molecule drugs and biologics, known drugs, and the extent of previously described associations with pain in the literature. In addition, the TenZero team has reviewed the literature for all red box proteins.
Repurposing and Validation Existing approved drugs have been identified for a number of our red box proteins. For two of these drugs, early outcomes have been positive, and one is being investigated in an ongoing clinical trial. Beyond repurposing - which TenZero may pursue in coordination with NDA holders - these results validate TenZero's approach to target identification. Moreover, patients have, in some cases, reduced their use of opioids.
Novel Therapeutics TenZero has selected a number of targets as the core of its internal drug discovery and development program. TenZero is initiating collaborations with class-leading companies that are driving a revolution in AI-enabled drug discovery and development. In addition to its in-house programs, TenZero is seeking collaborations with pharmaceutical and biotechnology companies that are committed to finding new ways to treat pain and improve patients’ quality of life.
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