Laryngo-Onycho-Cutaneous Syndrome (LOCS), an extremely uncommon ailment, results from mutations in the genes LAMA3, LAMB3, or LAMC2, which result in production of laminin-332 and epithelial fragility. Defect severity depends on LOCS. Protheragen provides comprehensive preclinical LOCS drug and therapy development services to hasten translational innovations.
Overview of Laryngo-Onycho-Cutaneous Syndrome
Also known as junctional epidermolysis bullosa (JEB)-laryngoonychocutaneous subtype, LOCS presents with chronic skin erosions, progressing nail dystrophy, and potentially fatal laryngeal involvement owing to laminin-332 deficiency. Among the rarest subtypes of epidermolysis bullosa, it's estimated incidence is <1 in 1,000,000 live births. Recent research underscores the importance of the epithelial-mesenchymal interactions and impaired wound healing as central to its progressive pathology.
Fig.1 Variants identified in LAMB3 and corresponding phenotypes. (Wen
et al., 2024)
Diagnostic Development for Laryngo-Onycho-Cutaneous Syndrome
Genomic Profiling
Recent long-read sequencing studies have resolved complex structural variations in LAMA3 and LAMB3 genes, which encode laminin subunits critical for epithelial basement membrane integrity. Advanced CRISPR-based functional screens now validate the pathogenicity of non-canonical splice variants and deep intronic mutations, addressing previous diagnostic gaps in cases with atypical presentations.
Dynamic Proteomic Mapping
Mass spectrometry-based analyses reveal distinct depletion of laminin-332 isoforms in patient-derived keratinocytes, correlating with disrupted cell-matrix adhesion. Multi-omics integration (transcriptome-proteome) further identifies compensatory upregulation of integrin-α6β4 as a potential biomarker for disease stratification.
Therapeutics Development for Laryngo-Onycho-Cutaneous Syndrome
The current therapeutic approach for LOCS involves a multidisciplinary strategy that is still largely in the preclinical stage. It consists of gene-based therapy aimed at LAMA3/LAMB3 and corticosteroids, along with amniotic membrane grafts, to alleviate symptoms. The approach has not proven to be effective.
Table.1 Therapeutic Development of Laryngo-Onycho-Cutaneous Syndrome.
| Therapeutic Strategy |
Target |
Key Findings/Mechanism |
Development Stage |
| Gene Therapy (Lentiviral expression of wild-type LAMA3A) |
LAMA3 gene |
Restored cell adhesion, differentiation, and cilia production in airway cells with LAMA3 mutations. |
Preclinical |
| Topical and Systemic Corticosteroids |
Inflammation, Granulation Tissue |
Used for laryngeal stenosis, symblepharon, and paronychia with caution in children. |
Approved |
| Amniotic Membrane Transplantation |
Laminin α3a |
Partially effective for ocular issues by supplying healthy laminin α3a; longer follow-up showed recurrence in some. |
Approved |
| Gene Editing |
LAMB3 gene |
Corrected a common JEB-causing mutation in LAMB3, increasing laminin 332 and improving cell adhesion. |
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 focuses on building an ecosystem to prepare for the preclinical trials and builds integrated solutions aimed accelerating the preclinical development of LOCS. From therapeutic development, diagnostics development to disease model development, our specialists use sophisticated tools to provide all-sides assistance.
- LAMA3-KO Immortalized Keratinocyte Lines
- Patient-Derived Primary Mucosal Epithelial Cells
- Organoid-Based Mucosal Models
- Conditional Lama3 Knockout Mice
- Humanized LAMA3 Transgenic Mice
Bridging the gap between discovery and development, Protheragen concentrates on preclinical research with the purpose of expediting the discovery of potential drugs and therapies for LOCS. We provide complete in vitro and in vivo studies, including drug safety evaluation and DMPK services to make sure you make the best selection from your numerous drug candidate pools with the help of our sophisticated facilities and our scientific team.
Partner with us to LOCS research into viable therapeutic innovations. For inquiries regarding our comprehensive services, please contact us.
References
- Hemani, F., U. Khurram, and A. Naveed. "Laryngo-Onycho-Cutaneous Syndrome (Locs)." Pak J Med Sci 40.2ICON Suppl (2024): S100-S02.
- Wen, D., et al. "Genotype-Phenotype Correlation in Junctional Epidermolysis Bullosa: Signposts to Severity." J Invest Dermatol 144.6 (2024): 1334-43 e14.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
