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Acral Peeling Skin Syndrome (APSS)

Acral peeling skin syndrome (APSS) is a rare inherited skin disorder that leads to painless peeling of the outer layers of skin on the hands and feet, often beginning at birth or during early childhood. APSS is caused by genetic mutations that impair the cohesion of skin. Protheragen provides one-stop preclinical drug and therapy development services focused solely on providing solutions to the challenges of APSS.

Introduction to Acral Peeling Skin Syndrome

Acral peeling skin syndrome is an autosomal recessive genodermatosis that affects the epidermis, resulting in superficial, painless peeling of skin on acral surfaces, primarily on the palms and soles. It often appears at birth or in early childhood. Although the actual prevalence is not known, APSS is uncommon and reported globally across multiple ethnic groups.

Pathogenesis of Acral Peeling Skin Syndrome

APSS occurs primarily due to the genetic mutations affecting the proteins responsible for cohesion of skin cells and the epidermal barrier. The most commonly implicated gene in APSS is TGM5, which codes for transglutaminase 5, an enzyme that is important in creating a cornified cell envelope in the outermost layer of skin. Mutations in TGM5 will result in decreased or absent activity of the enzyme, which disrupts the crosslinking of structural proteins such as loricrin and involucrin. This malfunction results in corneocytes (the dead skin cells of the stratum corneum) being less stable and adhere less to the underlying layers, leading to spontaneous painless peeling of the outer layers of skin on the hands and feet for persons with APSS.

Fig.1 Splitting between the stratum granulosum and corneum and within the horny layer of epidermis (arrows). (Krunic et al., 2013)

Therapeutics Development for Acral Peeling Skin Syndrome

Gene Therapy

Gene Therapy: There have been studies that show feasibility of using CRISPR-Cas9 to repair TGM5 mutations in keratinocytes derived from patients. For instance, in vitro studies have shown that gene correction restores TGM5 activity with improved cell adhesion and decreased skin peeling.

Cell Therapy

Cell Therapy: Recent studies have studied correction of TGM5 gene mutations in these iPSCs prior to differentiating into functional keratinocytes. In addition, bioengineered skin substitutes derived from these corrected keratinocytes have been developed and tested in vitro and in animal studies.

Our Services

Protheragen a comprehensive range of services to facilitate advancement of therapeutics for acral peeling skin syndrome. Our team of scientist, dermatologists and geneticists are currently developing to accelerate advancement using cutting-edge technologies with specialized therapeutic development and disease model development services to support your projects.

Therapeutic Development Services

Disease Model Development Services

Tgm5 Knockout Mouse Models
Csta Knockout Mouse Models
Tgm5 Missense Mutation Knock-in Mouse Models
Csta Missense Mutation Knock-in Mouse Models
Tg(KRT14-TGM5) Transgenic Mice

As a full-service preclinical research partner, Protheragen specializes in accelerating therapies for rare skin diseases, including acral peeling skin syndrome. Our integrated platform spans target validation and disease modeling to drug safety evaluation and DMPK services, leveraging tailored in vitro and in vivo models to address APSS-specific challenges.

If you are interested in our services, please feel free to contact us.

References

Krunic, A. L., et al. "Acral Peeling Skin Syndrome Resulting from a Homozygous Nonsense Mutation in the Csta Gene Encoding Cystatin A." Pediatr Dermatol 30.5 (2013): e87-8.
van der Velden, J. J., et al. "A Recurrent Mutation in the Tgm5 Gene in European Patients with Acral Peeling Skin Syndrome." J Dermatol Sci 65.1 (2012): 74-6.

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