Hailey-Hailey Disease (HHD)

Hailey-Hailey Disease (HHD) is a rare hereditary condition which manifests as painful blisters or erosions predominantly around the neck region, the armpits, and the groin due to mutations in ATP2C1 gene. Protheragen provides complete preclinical drug and therapy development services for HHD which helps in the translation of the research into therapeutic modalities.

Introduction to Hailey-Hailey Disease

The mutations of ATP2C1 gene are responsible for HHD and result in abnormal hereditary (autosomal dominant) changes to skin tissues, distinguishing it as autosomal dominant genodermatosis. Each occurrence is said to result in a ratio of 1:50000. Recent research has started focusing on other primary pathological causes such as dysfunctional autophagy and oxidative stress which worsen acantholysis and the chronic accompanying inflammation.

Hailey-Hailey Disease

• Genetic Mutation and Calcium Dysregulation: The disabling mutations on the hSPCA1 calcium pump ATP2C1 give rise to HHD. The resulting mutations have direct impact on calcium transport and therefore disrupt keratinocytes cellular calcium levels which leads to calcium homeostasis deviation, this deficiency is termed the primary molecular defect of HHD.
• Disrupted Cell Adhesion and Acantholysis: Acantholysis, or the splitting of keratinocytes, occurs as a result of weakened cell-cell adhesion due to a deficit in intracellular calcium. This leads to a decrease in the formation and stability of desmosomes, the structures that anchor keratinocytes together. This injury gives rise to the blisters and erosions associated with HHD.

Fig.1 Molecular pathogenesis of Hailey-Hailey Disease (HHD). (Sardana et al., 2024)

Therapeutics Development for Hailey-Hailey Disease

Therapeutic strategies for Hailey-Hailey Disease focus on symptom control, mitigation of disease exacerbations, and management of the underlying molecular defect.

Table.1 Commonly recommended therapies for Hailey-Hailey Disease. (Farahnik et al., 2017)

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 provides full service to develop therapies aimed at rare skin conditions such as Hailey-Hailey Disease. Our specialists, including scientists, dermatologists, and geneticists, are dedicated to the development of therapeutic and disease model to support research in every stage of the research project.

Therapeutic Development Platforms for Hailey-Hailey Disease

Disease Model Development for Hailey-Hailey Disease

Protheragen specializes in custom 2D cell models and 3D skin models which provide relevant molecular pathological study features in Hailey-Hailey Disease like calcium signaling perturbations and acantholysis. Our animal models showcase the hallmark symptoms of HHD such as skin fragility, blistering, and erosions which serves as a robust proof of concept for drug candidates aimed at restoring cell adhesion and inflamed cell signaling pathways.

As a preclinical research services provider, Protheragen seeks to spearhead the development of therapeutics aimed at rare skin diseases such as Hailey-Hailey Disease. Due to our proprietary model, there is ease of implementation from target discovery, disease modeling, and advanced drug safety evaluation and DMPK services. If you are interested in our services, please feel free to contact us.

References

• Farahnik, B., et al. "Interventional Treatments for Hailey-Hailey Disease." J Am Acad Dermatol 76.3 (2017): 551-58 e3.
• Sardana, K., et al. "Therapeutic Agents for Hailey-Hailey Disease: A Narrative Review." Indian J Dermatol Venereol Leprol (2024): 1-8.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.