Photodynamic Therapy as a new approach for the treatment of herpes simplex virus infections

The present thesis aims to explore the application of Photodynamic Therapy (PDT) for the treatment of herpes simplex virus (HSV) infections. PDT is a minimally invasive technique that requires the activation of a photosensitizer molecule through light exposure. This leads to the production of reactive oxygen species (ROS) within the cells, resulting in damage to the targeted areas where the photosensitizer has accumulated. PDT has emerged as a modern approach arising in clinical practice for disrupting cancerous tissues, as well as deactivating bacteria, fungi, and viruses. Furthermore, PDT possesses the capability to stimulate the host immune system. This work focuses on the impact of PDT on HSV, an enveloped virus that once infects keratinocytes causes the so-called herpes labialis or genitalis. Subsequently, the virus establishes latency within sensory neurons. However, different stimuli can interrupt this state leading to viral reactivation and recurrent infections, typically occurring 2-3 times per year. The virus spreads worldwide by direct contact and has no seasonal variation. Despite the self-limiting nature of the disease, complications and hypersensitivity reactions cannot be excluded, and together with the emergence of resistance to antivirals, PDT is being exploited as a promising new approach for managing the diseases. The primary objective is to identify optimal photosensitizers that can selectively target the affected areas while demonstrating minimal toxicity to surrounding cells. Recently, the application in vitro of Orthoquin and 5-Aminolaevulenic Acid as photosensitizers has been investigated, showing that the presence of the virus is reduced after treatment on model cells. Moreover, the first clinical trial involving the combination of the photosensitizer Methylene Blue and the antiviral Acylcovir demonstrated statistically significant differences in key parameters such as viral load and pro-inflammatory biomarkers for the group treated with PDT as an adjunct therapy. To date, further clinical trials still need to be conducted, and protocols must be established. However, mounting evidence suggests the potential of PDT as a non-invasive adjunctive treatment to conventional therapies.