U of T prof starts Reflexion Pharmaceuticals to make new class of “mirror image” molecules
When you look into a mirror what you see is not a true image of yourself but rather a “reflection.” For example, the eye you see in the mirror directly across from your right eye is now on the left side of your face in the mirror. If you were to take a photograph of your image in the mirror, you couldn’t superimpose it onto a normal picture of yourself.
This same phenomena can occur on the molecular level. It’s possible to make two proteins that are exact mirror images, or “reflections,” of each other. In nature, proteins are made of L-amino acids. However, if you make proteins using the mirror image D-amino acids you can make the exact mirror image of a protein. These mirror image proteins aren’t recognized by the enzymes that naturally degrade proteins or by the immune system, so they can hang around longer in the body, potentially making them more effective as drugs.
Professor Sachdev “Dev” Sidhu of molecular biology has started a company, appropriately named Reflexion Pharmaceuticals, to make an entirely new class of drug molecules in mirror image form. In addition to evading the body’s usual ways of eliminating drugs, Reflexion’s drugs are made chemically at a fraction of the cost of making traditional biologic drugs.
The core technology, which the company licensed from the Whitehead Institute, involves first making a mirror image of the protein to which the drug will bind (the target protein). Dr. Sidhu then uses his expertise in molecular and phage library design to find a protein that can bind to and inhibit the activity of the target protein. By then making the mirror image of the protein he’s discovered, he can inhibit the original, non-mirror, target protein. Dr. Sidhu, together with U of T postdoctoral fellow Maruti Uppalapati, has successfully used this technique to discover a novel mirror image inhibitor of vascular endothelial growth factor (VEGF), a protein which stimulates new blood vessel growth.
There are several approved drugs that inhibit VEGF and are used to treat a variety of serious diseases, including colon, kidney, lung and breast cancers and the eye disease, including wet age-related macular degeneration, the leading cause of blindness in the developed world. The currently marketed VEGF-inhibiting drugs generate over $10 billion in annual revenues.
The first step in Reflexion’s drug discovery process is to make the target protein in mirror image form, something that can only be done chemically. For this, Dr. Sidhu teamed up with Reflexion co-founder and U of Chicago professor, Stephen Kent.
Dr. Dana Ault-Riché, Reflexion’s CEO says, “Steve is the best person in the world at making proteins using chemistry and Dev is the best phage library designer, so Reflexion has the two best people it could possibly have joining forces to make its technology work.”
In addition to cancer and eye diseases, Reflexion has plans to use its technology to make drugs for a variety of other conditions including inflammatory diseases like arthritis and osteoporosis, infectious diseases and chronic pain.