Lipoid Proteinosis (LP) or Urbach-Wiethe disease is a rare autosomal recessive genetic disorder caused by mutations on the ECM1 gene which incur the accumulation of hyaline material in different body tissues. Protheragen offers innovative drug and therapy development for lipoid proteinosis, providing comprehensive solutions to accelerate translation of research into effective therapies.
Introduction to Lipoid Proteinosis
Lipoid Proteinosis is an extremely rare condition due to its abnormal accumulation of a particular type of hyaline material in peripheral tissues such as skin and mucous membranes and some internal organs. This results in skin thickening and scarring along with severe hoarseness owing to the involvement of the vocal cords. This is also the result of a mutation in the ECM1 gene leading to an insufficient production of extracellular matrix protein 1. The incidence of lipoid proteinosis is estimated to be less than 1 in 1,000,000 people worldwide.
Pathogenesis of Lipoid Proteinosis
The mutations in the ECM1 gene associated with lipoid proteinosis results in an absence of extracellular matrix protein 1, and this deficiency greatly impacts the structure and function of the extracellular matrix within the skin and mucous membranes, culminating in abnormal deposition of hyaline-like collagen and laminin. This material deposition is the underlying cause of tissue inflammation and calcification which is associated with the hallmark features of the disease, such as skin lesions, hoarseness due to vocal cord involvement, and other mucosal changes.
Fig.1 Advances in treatment for lipoid proteinosis. (Bueno-Molina
et al., 2024)
Therapeutics Development for Lipoid Proteinosis
Gene Therapy and Genome Editing
Development efforts have been directed at gene therapy aimed at lipoid proteinosis targeting the ECM1 gene with the aim of correcting the gene's mutations. Work is being done on strategies to fix the erroneous gene. There is some hope of restoring the function of ECM1 in cell model systems as preclinical studies have provided some hope for future clinical use.
Recombinant ECM1 Protein Replacement
Research focuses on ECM1 recombinant protein use in substitution therapies. The goal of administering synthetic ECM1 is to restore function of the extracellular matrix which the disease disrupts. Initial studies and advances in protein engineering and delivery systems indicate this approach could help, at least to some extent, in reducing hyaline deposition and ameliorating symptoms.
Small Molecule Therapies
Research is also aimed at developing small molecule drugs that alter pathogenic pathways. Using high-throughput screening, several compounds have been selected that inhibit deposition of hyaline material or enhance ECM1 expression. These studies aim to fine-tune these compounds for efficacy and safety, with the goal of reducing disease progression.
Our Services
Protheragen provides comprehensive therapeutic development and disease model development services to advance lipoid proteinosis therapy. Our team of scientists, dermatologists, and geneticists utilizes sophisticated technologies specific to the disorder to assist in developing effective therapies.
Therapeutic Development Platforms for Lipoid Proteinosis
Protheragen's platforms integrate small molecule therapeutics for modulating abnormal extracellular matrix deposition, gene therapy techniques for targeted ECM1 correction to restore normal protein function, and biologics to reduce tissue thickening and improve skin and mucous membrane health associated with lipoid proteinosis.
Disease Model Development for Lipoid Proteinosis
Protheragen has developed preclinical models for lipoid proteinosis, including 2D cell models, 3D skin models, and animal models that capture relevant pathophysiological features of the disease and aid in developing potential therapies.
- Patient-Derived Fibroblasts and Keratinocytes
- ECM1 Mutant Cell Lines
- Organotypic Skin Equivalents
- ECM1 Knockout Mice
- Transgenic Mice with ECM1 Mutations
- Conditional ECM1 Knockout Mice
Protheragen provides preclinical research services targeted to the specific pathology of lipoid proteinosis caused by ECM1 mutations. We can provide end-to-end services from discovery through disease modeling and regulatory based drug safety evaluation and DMPK services. If you are interested in our services, please feel free to contact us.
References
- Bueno-Molina, R. C., et al. "Advances in Treatment for Lipoid Proteinosis (Urbach-Wiethe Disease): A Case Report and Systematic Review." Clin Exp Dermatol 49.6 (2024): 547-55.
- Verma, D., et al. "Lipoid Proteinosis: A Rare Case Report and Review of Literature." Indian Dermatol Online J 15.5 (2024): 866-69.
- Zhang, B., et al. "Microwave Treatment Ameliorates Beaded Eyelid Papules Caused by Lipoid Proteinosis." Pediatr Dermatol 41.6 (2024): 1248-50.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
