ProMIS™ and Disease Specific Epitopes™ (DSE)
The challenge in detecting and treating misfolded proteins is distinguishing them from normal proteins. Amorfix's ProMIS™ target identification technology is an in silico rational selection approach to identity unique regions found on the molecular surface of misfolded proteins called Disease Specific Epitopes™ (DSE) that are not found on the normal protein.
Using only partial information about the 3D native structure, ProMIS™ can predict the misfolded conformation of the protein including motifs that become exposed. In diseases where the misfolded protein and not the normal structure is implicated in the pathology, as in the case with the SOD1 protein in ALS, designing antibodies that are specific for the misfolded form is very valuable for both therapeutic and diagnostic purposes.
Antibodies generated to the predicted DSEs have several potential advantages over the traditional antibody targeted therapy strategy, including specificity to the pathogenic misfolded protein species, and safety by avoiding interactions with the normal protein. For example, in cancer treatments where immunotherapies have been problematic due to side effects by cross reactivity with healthy cells, targeting DSEs on transmembrane misfolded proteins using ProMIS™ antibodies will treat only the diseased cells.
Diagram: Amorfix Therapeutic Strategy
Amorfix's therapeutic platform involves therapeutic antibodies (red), which are designed to differentiate between normally folded proteins and disease-causing misfolded proteins. The antibodies bind specifically to the misfolded proteins and neutralize them.
- Structural information about a given protein is analyzed using the ProMIS™ algorithm
- Regions of the protein likely to misfold, or disease specific epitopes (DSE), are identified (green).
- Therapeutic antibodies are made against these DSEs.
- The DSEs can be targeted by Amorfix's antibodies when the protein misfolds. The antibodies only recognize the misfolded form and do not bind to the normally folded proteins.