Psoriasis is a long-lasting skin condition characterized primarily by skin-related symptoms such as dryness, itching, flakiness, and irregular patches or plaques. Around 2% of individuals are affected by this ailment, which is caused by a dysfunctional immune response that stimulates an excessive growth of skin cells. There are various treatment options available based on severity (including topical creams, light therapy, systemic medications, etc.), although some traditional treatments may pose negative side effects for patients.
A recent study conducted by the University of Barcelona has confirmed the effectiveness of a novel compound for treating psoriasis, which may help mitigate the associated risks linked to existing therapies. The research indicates that a molecule activated by blue light, known as MRS7787, can regulate immune system activity and effectively treat psoriasis in animal models. This marks a significant breakthrough in the realm of photopharmacology, a precise scientific field focused on drugs called photopharmaceuticals, which can be activated or deactivated by light exposure.
Published in the Journal of the American Chemical Society, the study is spearheaded by Francisco Ciruela, a professor at the Faculty of Medicine and Health Sciences at UB, and a member of the Institute of Neurosciences (UBNeuro) and the Bellvitge Biomedical Research Institute (IDIBELL). The lead author of the paper is Marc López-Cano, with significant contributions from Concepció Soler (UB, UBNeuro, and IDIBELL) and Jordi Hernando (Universitat Autònoma de Barcelona), among several other experts including Kenneth Jacobson from the National Institutes of Health (NIH) and Dirk Trauner from the University of Pennsylvania.
A Photopharmaceutical Approach to Psoriasis Treatment
The research team at UB has thoroughly examined the new compound MRS7787, a light-activatable molecule that attaches to the A3 adenosine receptor, which plays a role in several intracellular signaling pathways, producing an anti-inflammatory effect. MRS7787 exists in two forms, or isomers—molecules with the identical chemical formula but differing structures and functions—that can swiftly and reversibly change due to light exposure.
Ciruela explains that “MRS7787 is a photo-switchable molecule. One version, Z-MRS7787, is inactive, while the E-MRS7787 version activates the adenosine receptor.” He elaborates that “when exposed to blue light, the molecule shifts from the Z to the E configuration, that is, into its active form. However, when exposed to green light, the E configuration converts back to Z, thereby inactivating the compound.” “This transformation is facilitated by a covalently linked photochrome called diazocine to the A3 adenosine receptor,” according to the UB researcher from the Department of Pathology and Experimental Therapeutics.
“The unique feature of the diazocine photochrome is that it allows the photopharmaceutical MRS7787 to remain in its inactive Z configuration in darkness, enabling it to be injected without any photopharmacological reaction occurring, and then selectively activated by exposure to blue light,” adds Jordi Hernando from the Department of Chemistry at the Universitat Autònoma de Barcelona, who was responsible for studying the photochemical properties of MRS7787.
The E-MRS7787 version can activate the A3 adenosine receptor without interfering with the activity of other adenosine receptors. “This specific activation has an anti-inflammatory effect and reduces the release of pro-inflammatory cytokines by immune cells. Therefore, activating this receptor is an effective strategy for managing inflammatory conditions in general, particularly in treating psoriasis,” states expert Marc López-Cano (UB, UBNeuro, and IDIBELL).
In the course of the study, MRS7787 was administered to animal models, followed by an eight-minute exposure of a targeted area—specifically, the ears, where inflammation was induced—with an LED device. One ear received blue light at an intensity of 1.18 mW/cm2, while the other was exposed to green light at 7.64 mW/cm2. Results showed that the Z-MRS7787 isomer derived from green light exposure exhibited no anti-psoriatic effects, unlike E-MRS7787, thereby indicating that the therapeutic effectiveness is reliant on the photoswitching mechanism of the molecule.
Exploring Combined Treatments for Patients
Topical corticosteroids, keratolytic agents, calcineurin inhibitors, and vitamin D analogs are commonly used for mild psoriasis treatment. More extensive cases that affect larger skin areas are often treated with biologic therapies or oral chemical medications. “Typically, these latter two treatment types can be combined with localized or generalized phototherapy, which involves exposing the skin to ultraviolet (UV) rays of certain wavelengths. This general phototherapy can be enhanced with a treatment known as PUVA, which combines a psoralen oral medication with UVA exposure. However, long-term use poses a risk of skin cancer,” explains López-Cano.
The photopharmaceutical MRS7787 presents new possibilities for enhancing treatment efficacy in the multimodal management of psoriasis, particularly for treatment-resistant cases, while minimizing adverse effects from conventional therapy. “Combining MRS7787 with PUVA therapy could improve treatment outcomes and reduce side effects (like skin cancer). The use of this multimodal phototherapy could streamline the treatment process, as the light exposure would be administered once daily, sustaining anti-psoriatic effectiveness and boosting patient adherence to treatment,” the specialists suggest.
MRS7787 is derived from piclidenoson, a compound that is non-photosensitive and also selectively interacts with the A3 adenosine receptor, currently undergoing phase 3 clinical trials for treating rheumatoid arthritis and psoriasis. The researchers aim to validate this novel drug target for other inflammatory diseases, such as arthritis or pain linked to inflammatory conditions, to expand its potential pharmacological applications and clinical relevance.
