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X-linked Recessive Ichthyosis (XLI)

X-linked Recessive Ichthyosis (XLI) or steroid sulfatase (STS) deficiency is one of the more prevalent genetic skin disorders that features extensive scaling of the skin. This condition has an X-linked pattern of inheritance and occurs almost exclusively in males. Protheragen provides sophisticated preclinical drug and therapy development services for X-linked Recessive Ichthyosis.

Overview of X-linked Recessive Ichthyosis

X-linked recessive ichthyosis (XLI) is a rare genetic condition affecting the skin, estimated to occur in 1 out of every 2,000-6,000 males which is caused by deletion or mutation on STS gene located at Xp22.3 resulting in steroid sulfatase deficiency. XLI emerges with dark polygonal scales on extremities and trunk that present at birth along with collodion membrane or generalized scaling. In contrast to other autosomal forms of ichthyoses, XLI has unique features which include corneal opacities and elevated maternal serum estriol substantiating pregnancy complications.

Schematic overview of metabolic pathways for phytanate metabolism.

Fig.1 Potential approaches to understand the pathophysiology of extracutaneous phenotypes associated with X-linked ichthyosis (XLI). (Wren and Davies, 2022)

Pathogenesis of X-linked Recessive Ichthyosis

Disorders associated with X-linked Recessive Ichthyosis (XRI) emerge from mutations or deletions within the STS gene, causing a deficiency of the steroid sulfatase enzyme. This weakens the enzyme's activity leads to an excessive accumulation of cholesterol sulfate in the stratum corneum layer of the epidermis. The excess in cholesterol sulfate derangements normal desquamation, thereby leading to dark adherent scales and impaired barrier function of the skin seen in affected individuals.

Therapeutics Development for X-linked Recessive Ichthyosis

Therapeutic Strategy	Target	Key Findings/Mechanism	Development Stage
Simvastatin	HMG-CoA reductase	Inhibits cholesterol sulfate synthesis	Phase II
T4 Endonuclease V (T4N5) Liposomes	UV-induced DNA damage	Repairs cyclobutane pyrimidine dimers; compensates photosensitivity	Phase III
KB105 (HSV-1 vector)	STS gene	Topical delivery of functional STS to epidermis	Phase I/II
Retroviral STS vector	STS gene	Transduction of keratinocytes for epidermal reconstruction	Preclinical to Phase I
Imsidolimab (anti-IL-36R)	IL-36 receptor	Blocks IL-36-mediated keratinocyte inflammation	Phase II
Baricitinib	JAK/STAT pathway	Inhibits IFN-γ signaling; reduces autoimmune skin inflammation	Phase II

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 comprehensive integrated services for the innovation of X-linked Recessive Ichthyosis, including therapeutic development, diagnostics development, and disease models to facilitate the translation of therapeutic solutions. Via advanced platforms, we guarantee seamless transitions from discovery to IND-enabling studies.

Therapeutic Development

Diagnostics Development

Biomarker Development
Single-Cell Spatial Transcriptomics
Steroid Sulfatase Proteomic Profiling
Diagnostic Kit Development
Multiplex NGS Panels for STS Variants
Point-of-Care STS Enzyme Activity Assays

Disease Model Development

Fibroblasts/Keratinocytes with STS Mutations
STS Knockout (KO) Keratinocytes
STS-Deficient Reconstructed Human Epidermis
Sts^-/- Mouse Models
Sts Conditional Knockout Mice

Drug Safety Evaluation & DMPK Services

In Vitro ADME Services

Metabolic Stability
Reaction Phenotyping
Plasma Protein Binding
Blood/Plasma Partitioning

In Vivo Pharmacokinetics Services

Single-Dose PK Studies
Multiple-Dose PK Studies
Bioavailability and Bioequivalence Studies
Tissue Distribution Studies

Drug Safety Evaluation

Protheragen stands out by seamlessly applying advanced in vitro and in vivo technologies to expedite the preclinical development of XLI therapeutics. The integration of our services, such as drug safety evaluation and DMPK, supports the rapid optimization of strategies targeting cholesterol sulfate metabolism modulation and restoration of STS enzyme function for more detailed mechanistic and translational studies.

Partner with us to transform X-linked Recessive Ichthyosis research into viable therapeutic innovations. For inquiries regarding our comprehensive services, please feel free to contact us.

References

Wakumoto, K., Y. Yoshida, and O. Yamamoto. "Is X-Linked Recessive Ichthyosis a High Risk for Basal Cell Carcinoma?" Yonago Acta Med 63.1 (2020): 92-94.
Wren, G. H., and W. Davies. "X-Linked Ichthyosis: New Insights into a Multi-System Disorder." Skin Health Dis 2.4 (2022): e179.

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