Light and medicine have a long and intertwined past. Most civilizations throughout history appear to have understood that there was a connection between sunlight and good health. The ancient Egyptians worshipped the sun, with Ra the sun god often described as the king of all gods. Both the ancient Romans and Greeks used sunbaths to maintain good health. Heliotherapy (helio is Greek for sun) was deemed an important part of athletic training in ancient Greece as it was thought to improve muscle health.The link between light and medicine was exemplified by Niels Finsen a pioneer of modern phototherapy. Finsen was awarded the 1903 Nobel Prize in Physiology or Medicine in recognition of his contribution to the treatment of diseases, especially lupus vulgaris, with concentrated light radiation, whereby he has opened a new avenue for medical science.

By the end of the first quarter of the 20th century, the use of phototherapy for medical purposes, in northern Europe and some regions of North America, was considerable. Prof. Dirk Trauner says that whist phototherapy has been hugely successful, the chemistry that currently mediates the effects of light in phototherapy is relatively simple.

Trauner and his team set out to develop more sophisticated ways to harness light therapeutically. We have been joined in this effort by a growing number of colleagues, explains Trauner. Ben L. Feringa is one such colleague, who was jointly awarded the Nobel Prize in Chemistry for the design and synthesis of molecular machines in 2016.

Trauners work is based photopharmacology, an innovative approach whereby light is used to activate and deactivate therapeutics and/or biological processes.

However, by introducing photopharmacology, Trauner explains that it is possible to add a further level of control to the PROTAC. One can target their [PROTACS] action to specific tissues or tumors, avoiding side effects elsewhere in the body, says Trauner.

Whilst phototherapy is typically applied to the surface of the skin, PHOTACs could be switched on and off within the body by means of an endoscope combined with a light source, or by using an implanted LED.

Furthermore, in future, by using different colors of light a concept known as color dosing it could be possible to control the activity of PHOTAC-based therapeutics even more precisely. By regulating the concentration of the active or switched-on form of the PHOTAC, dosage of the drug could be altered within the body gradually.

PHOTACs do work like PROTACS but can be activated or inactivated at will as long as light-delivery is possible. Light-delivery in the human body has become quite sophisticated in recent years. New technologies for light delivery are emerging, largely driven by optogenetics and photodynamic therapy, concludes Trauner.

Reference: Reynders, et al. (2020). PHOTACs enable optical control of protein degradation. Science Advances. DOI: 10.1126/sciadv.aay5064Dirk Trauner was speaking with Laura Elizabeth Lansdowne, Senior Science Writer for Technology Networks.

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Photopharmacology Switching Drugs On and Off With Light - Technology Networks