Limb-Mammary Syndrome (LMS) is a genetic condition that occurs as a result of a rare and often underdiagnosed mutation in p63 within a group of conditions referred to as ectodermal dysplasias. Protheragen concentrates on preclinical IP development projects through complex molecular pathology and therapeutic innovation of LMS.
Introduction to Limb-Mammary Syndrome
Limb-Mammary syndrome is a rare form of syndrome caused by the dominant disorder which occurs due to the mutations of the TP63 gene. LMS is registered to have an incidence of 1 in 100,000 globally and is associated with symptoms including skin, hair and teeth ailments. The syndrome is majorly witnessed and seen swiftly in woman. Usage of specific therapies is crucial in dealing with regenerative and developmental pathways.
Pathogenesis of Limb-Mammary Syndrome
- Dysregulation of the TP63: This specific gene is responsible for the production of the transcription factor p63 to ensure there is a proper and non-problematic flow of epithermal stem cell as well as limb cannon development. Synthesis issues or dsyfunction lead to delays and termed failure in mammary cell apoptosis headway.
- Developmental defects: Either Hypohidrosis or moving to secondary displacement resulting in multiple dental issues can occur due to broken p63 control.
- Secondary complications: Pediatric obstetric and infant incurable infection, repetitive bone weakening, jaw ilusios, and social problems due to advanced deformities are some of the side effects of chronic skin ulceration.
Fig.1 Domains of TP63 gene and genotype-phenotype correlation. (Sogukpinar
et al., 2024)
Therapeutics Development for Limb-Mammary Syndrome
Table.1 Therapies for Limb-Mammary Syndrome.
| Therapeutic Strategy |
Target / Intervention |
Key Findings / Rationale |
Development Stage |
| Gene Therapy |
Delivery of a functional TP63 gene copy to affected cells. |
Aims to correct the underlying genetic defect by providing a normal gene to restore proper p63 protein function in development. |
Preclinical |
| Gene Editing |
Direct correction of the mutated TP63 gene in patient cells using technologies like CRISPR-Cas9. |
Offers the potential for a permanent correction of the genetic mutation, restoring the normal DNA sequence and p63 protein function. |
Preclinical |
| Small Molecule Inhibitors/Activators |
Mutant p63 protein; Downstream signaling pathways dysregulated in LMS. |
Seeks to modulate the activity of the mutant p63 protein, either enhancing its function if it's a loss-of-function mutation or inhibiting it if it's a gain-of-function mutation. |
Preclinical |
| Protein Therapy |
Delivery of functional p63 protein to affected tissues. |
Could potentially compensate for the lack of functional p63 protein in individuals with loss-of-function mutations. |
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 complete service in developing therapies that focus on rare skin diseases such as limb-mammary syndrome. Our developed specialists, which include scientists, dermatologists, and geneticists, work on developing therapeutic and disease model to support research for all stages of the research project.
Therapeutic Development Platforms for Limb-Mammary Syndrome
Disease Model Development for Limb-Mammary Syndrome
Protheragen has custom 2D cell models and 3D skin models that replicate the molecular pathology of limb-mammary syndrome, including p63 signaling dysfunction and developmental defects in limb patterning and ectodermal integrity. Our animal models exhibit key features of LMS, which make them suitable for testing therapies aimed at restoring p63 function, promoting tissue regeneration, and managing ectodermal defects.
- Patient-Derived TP63-Mutant Keratinocytes
- HaCaT-ΔTP63 Cell Lines
- TP63-Mutant Reconstructed Human Epidermis
- TP63-Mutant Dermal Fibroblasts
- Conditional Tp63 Knockout Mice
- Humanized TP63 Truncation Mice
- TP63+/- Mice with Ectodermal Focus
- TP63-Mutant Skin Xenograft
As a preclinical research services provider, Protheragen pioneers therapeutic development for rare dermatological conditions like limb-mammary syndrome. Leveraging our proprietary disease models and end-to-end platforms, we streamline workflows from target discovery and disease modeling to drug safety evaluation to DMPK services. If you are interested in our services, please feel free to contact us.
References
- Guazzarotti, L., et al. "A Novel Stop Codon Variant Affecting Deltanp63 Isoforms Associated with Non-Syndromic Limb-Mammary Phenotype and Uterine Cervix Dysplasia." Clin Genet 99.3 (2021): 486-87.
- Sogukpinar, M., et al. "A Spectrum of Tp63-Related Disorders with Eight Affected Individuals in Five Unrelated Families." Eur J Med Genet 68 (2024): 104911. Print.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
