Researchers are increasingly exploring therapies that act strictly on the affected area, in order to reduce the adverse effects of the treatments. In the case of skin diseases, where direct access to tissue is possible, precisely controlling the activation of a drug could change the way common and difficult-to-treat conditions are approached.
A study demonstrates the potential of light-activated drugs to treat psoriasis without adverse effects. A group of Spanish researchers from the Institute for Advanced Chemistry of Catalonia (IQAC) of the Spanish National Research Council (CSIC) has developed a series of light-activated drug candidates that could become a therapeutic option for psoriasis.
The study supports the idea that photodynamic therapy, an advanced form of treatment that uses light to activate a photosensitive drugcan be used to locally activate systemically administered drugs.
This strategy could enable more targeted and less invasive treatments for skin diseases, including psoriasis.
The research was carried out in collaboration with the Bellvitge Biomedical Research Institute (IDIBELL), the Neuroscience Institute of the University of Barcelona (UBneuro), Johns Hopkins and Purdue universities in the United States, as well as the pharmaceutical company Eli Lilly.
Photosensitive drug molecules have no biological effect in the administered form, but change their structure when exposed to certain types of light.
This modification allows them to act on target receptors only in the areas targeted by the light. Thus, the therapeutic effect can be controlled from the outside, with greater precision, which reduces the risk of adverse reactions and opens perspectives for very specific treatments in areas such as pain, cancer or neurodegenerative diseases.
One of the major limitations of photodynamic therapy is the low penetration of light into tissues. For this reason, the skin is considered the most accessible tissue for such therapies. At the same time, many dermatological conditions continue to need effective and affordable treatments.
Psoriasis is one of the most common and disabling inflammatory skin diseases, affecting approximately 3% of the population. Around 30% of patients currently do not benefit from adequate and accessible treatments.
Although in recent years biological therapies have been approved for moderate and severe forms, they are expensive and are not indicated for localized psoriasis, considered the mild form of the disease. In addition, some patients have lesions in sensitive areas, where therapeutic options are limited.
Activation of the vitamin D receptor (VDR) is an approach known for its beneficial effects in psoriasis. However, the essential role of this receptor in calcium metabolism limits the clinical use of VDR agonists because of the risk of hypercalcemia, a potentially serious disorder that can lead to severe complications, including bone malformations.
Although there have been attempts to develop oral drugs to avoid these effects, none have yet reached the market.
In medical practice, topical treatments remain the most used, but their effectiveness is limited, and the difference between the effective dose and the one at which adverse reactions may occur is small, which requires medical monitoring.
The authors of the study pursued the design and synthesis of vitamin D receptor agonists that could be controlled by light. An optimized variant of the molecule, called PhotoVDRM, is inactive in the absence of light and can be selectively activated by exposure to certain wavelengths, including visible blue light, considered non-toxic, and UVB light, both of which are already used in dermatological treatments.
In vivo tests, carried out in animal models of psoriasis, showed a reduction of skin inflammation without the appearance of the usual adverse effects associated with systemic activation of the vitamin D receptor. The targeted activation of the drug produced a significant therapeutic effect without inducing systemic hypercalcemia (excess calcium in the blood), a major obstacle that has so far limited the clinical development of these treatments.
According to the researchers, this strategy based on photodynamic therapy opens the way to safer treatments targeting the vitamin D receptor. In the long term, the approach could be extended to other diseases mediated by this receptor, providing a general framework for the development of more precise treatments with an improved safety profile.
The results of this research were published in the journal ACS Central Science.
