Pseudoporphyria is a photosensitivity disorder that causes blistering, scarring, and fragile skin, often resembling Porphyria Cutanea Tarda (PCT) both clinically and histologically, but lacking the true porphyric biochemical changes. Protheragen specializes in the preclinical development of novel therapies for photosensitive skin disorders, including pseudoporphyria.
Introduction to Pseudoporphyria
Pseudoporphyria is an unusual condition that is caused by certain medicines or medical issues. The disorder is a type of photosensitivity condition that is very rare and acquired. People do not have any genetic faults with the heme biosynthesis pathway, so unlike in true porphyrias, there is no defect. Also, the levels of plasma and urinary porphyrin remains normal. It is often observed in those with certain underlying conditions like renal insufficiency or in those using drugs like naproxen, furosemide, or tetracyclines.
Fig.1 Hematoxylin-eosin staining of punch biopsy. (Clark
et al., 2024)
Pathogenesis of Pseudoporphyria
The pathogenesis of Pseudoporphyria is not fully understood, but is considered a combination of drug-induced photosensitization and oxidative stress. Some medications have the potential to absorb UV radiation, which can increase the production of reactive oxygen species (ROS) in the skin. Such ROS are capable of damaging cellular membranes, proteins, and even genetic material, leading to the hallmark skin lesions. In a number of instances, chronic renal insufficiency is associated with reduced photosensitive agents to be eliminated from the body and skin eventually led to the rise of these compounds within the skin. Such chronic oxidative stress results in dermal fibrosis, along with the destruction of the basement membrane zone, which accounts for the skin's increased fragility and scarring in the condition.
Therapeutics Development for Pseudoporphyria
| Therapeutic Strategy |
Drug Name |
Therapeutic Target |
Key Findings/Mechanism |
Development Stage |
| Glutathione Precursor |
N-Acetylcysteine (NAC) |
γ-Glutamylcysteine Ligase (GCLC) |
Activates GCLC to enhance glutathione synthesis; promotes skin lesion resolution |
Phase III |
| Direct Glutathione Supplement |
Reduced Glutathione |
Intracellular Glutathione (GSH) |
Intravenous administration improves skin fragility; synergistic effect with NAC |
Phase II |
| Complement Inhibitor |
Eculizumab |
Complement C5 (prevents MAC formation) |
Blocks membrane attack complex (MAC) formation; case reports show reduced blisters |
Preclinical |
| TLR4/NF-κB Pathway Inhibitor |
Baicalin |
TLR4/NF-κB signaling |
Suppresses UVA-induced ROS generation in vitro; efficacy in pseudoporphyria unverified |
Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen offers a comprehensive suite of preclinical solutions to accelerate therapeutic development for pseudoporphyria. Our team of specialists in dermatology, toxicology, and drug metabolism will work closely with your project leaders to advance therapeutic development and disease model development specifically tailored to this disorder, leveraging our state-of-the-art technologies.
Therapeutic Development Platforms for Pseudoporphyria
Protheragen's platforms integrate small molecule therapeutics targeting oxidative stress pathways, biologics aimed at mitigating inflammation and fibrosis, and specialized formulations for topical delivery. Our approach is designed to address the multifaceted pathogenesis of pseudoporphyria, from the molecular level to the skin phenotype.
Disease Model Development for Pseudoporphyria
Protheragen has significant expertise in developing and utilizing preclinical models for pseudoporphyria, which include 2D cell models, 3D skin models as well as animal models. These models recapitulate key pathophysiological features of the disease, such as drug-induced photosensitivity, oxidative damage, and dermal fibrosis, aiding in the evaluation of potential therapies.
- Drug-sensitized human keratinocytes
- UV-A primed dermal fibroblast model
- Drug-induced skin blistering organoid
- UV-A responsive epidermal equivalent
- NSAID-induced pseudoporphyria mouse
- Transgenic CYP2C9 metabolizer rat
DMPK and Drug Safety Evaluation Services for Pseudoporphyria
Protheragen's DMPK and drug safety evaluation services provide critical insights into how your drug is absorbed, distributed, metabolized, and excreted. Our services help to predict in vivo behavior and optimize dosing strategies for pseudoporphyria therapies, with a particular focus on skin tissue penetration of drug candidates.
In Vitro ADME Services
- Metabolic Stability
- Reaction Phenotyping
- CYP450 Inhibition/Induction
- Blood/Plasma Partitioning
- Transporter Interactions
Protheragen's expertise in rare skin disorders and drug-induced pathologies ensures seamless translation from target discovery to IND-enabling studies. We can provide end-to-end services from discovery through disease modeling to DMPK and drug safety evaluation services.
If you are interested in our services, please feel free to contact us.
References
- Clark, A., et al. "Olaparib-Induced Pseudoporphyria in a Patient with Ovarian Cancer." JAAD Case Rep 39 (2023): 58-60.
- Wang, Q., et al. "Drug-Associated Porphyria: A Pharmacovigilance Study." Orphanet J Rare Dis 19.1 (2024): 286.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
