Congenital Hypotrichosis with Juvenile Macular Dystrophy (CHJMD) is an uncommon condition that is inherited in an autosomal recessive manner. Protheragen provides integrated preclinical tools to understand the medical complexity of CHJMD and streamline therapeutic drug development.
Introduction to CHJMD
Congenital Hypotrichosis and Juvenile Macular Dystrophy (CHJMD) is an incredibly rare autosomal recessive disorder characterized by mutations affecting development of the hair and retinas. It has an incidence rate of < 1 in 1,000,000 people around the world. Reports of CHJMD are incredibly sparse and usually only in isolated areas or in consanguine families or isolated populations.
CHJMD is caused by mutations in the CNGB3 gene, which is known to have a role in cellular function, although the genetic basis of CHJMD is still being studied. CHJMD is extremely rare and the genetic characterization is sparse due to the rarity; CHJMD is the subject of focused genetic studies and this highlights the value of advanced diagnostic drinks. pidemiologic data is limited, indicating that additional population-based studies are warranted to understand the epidemiology and demographic patterns.
Fig.1 Identification of homozygous Alu-mediated deletion of exon 3 in the CDH3 gene, encoding cadherin 3. (Saeidian
et al., 2019)
Biomarkers Development for CHJMD
- Genetic Biomarkers: Identification of pathogenic variants in CNGB3 or associated genes serves as a primary biomarker for CHJMD diagnosis. Improved sequencing and advancements in whole-exome sequencing and gene panels enables babysitting autosomal recessive variants to assist genetic counseling and early identification of potential carriers.
- Molecular & Biochemical Biomarkers: Research focuses on measuring retinal disease specific proteins (e.g., photoreceptor-related factors) or metabolic changes in serum/plasma linked to macular degeneration. Proteomic and metabolomic profiling may probe disease-specific signatures correlating with progression or therapeutic response.
Therapeutics Development for CHJMD
Despite its rarity, congenital hypotrichosis with juvenile macular dystrophy has attracted interest in translational research, with strategies to provide therapeutic benefit including gene based therapy, pharmacology based therapy, and regenerative medicine.
Table.1 Therapeutic Development Pipeline for CHJMD.
| Therapeutic Approach |
Therapeutic Target/Goal |
Development Stage |
Key Studies/Evidence |
| Gene Replacement Therapy |
CNGB3 gene |
Preclinical |
AAV9-mediated delivery of CNGB3 restores ERG signals in mice |
| Gene Editing |
CNGB3 gene |
Preclinical |
Ex vivo correction of CNGB3 in patient iPSCs |
| Small Molecule (NRTIs) |
Mitochondrial inflammation |
Preclinical |
NRTIs inhibit cGAS-STING activation in CHJMD organoids |
| Stem Cell-Derived RPE |
Retinal structure restoration |
Preclinical |
iPSC-RPE transplants improve retinal layers in mice |
| Retinal Prosthetics |
Artificial vision restoration |
Preclinical |
PRIMA implant trials for AMD; CHJMD adaptation pending. |
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 a full testing service offering research services to advance development for congenital hypotrichosis with juvenile macular dystrophy. Our team of scientists, dermatologists and geneticists use and develop cutting edge technology for you to expedite the adoption of new therapeutic options for your disease; and provide specialized, focused therapeutic development and disease model development.
Therapeutic Development Platforms for CHJMD
Disease Models Development for CHJMD
Protheragen offers customized in vitro (2D cell models and 3D skin models) allowing to study unique molecular pathogenic processes associated with CHJMD, including defects in photoreceptor differentiation and alterations to retinal pigment epithelium (RPE) function. Our animal models faithfully reproduce classical disease phenotypes that resemble that of macular degeneration and congenital hypotrichosis allowing for strong in vivo validation of both gene therapies and small molecule therapeutics.
- Patient-Derived iPSC Photoreceptors
- Immortalized RPE Cell Lines (CNGB3−/−)
- CHJMD Retinal Organoids
- Dual-CNGB3-KO Retinal Organoids
- CNGB3 Knockout Mouse Model
- Conditional Retinal CNGB3-KO Mouse
- Humanized CNGB3 Knock-In Mouse
Protheragen is a one-stop preclinical research services provider who is committed to advancing therapeutics for rare skin diseases including congenital hypotrichosis linked with juvenile macular dystrophy. Our end-to-end solutions range from target discovery, disease modeling, and comprehensive drug safety evaluation and DMPK services. If you are interested in our services, please feel free to contact us.
References
- Liu, Y., et al. "Hypotrichosis with Juvenile Macular Dystrophy with Novel Mutations in Cdh3 Gene." Australas J Dermatol 65.1 (2024): 91-94.
- Saeidian, A. H., et al. "Hypotrichosis with Juvenile Macular Dystrophy: Combination of Whole-Genome Sequencing and Genome-Wide Homozygosity Mapping Identifies a Large Deletion in Cdh3 Initially Undetected by Whole-Exome Sequencing-a Lesson from Next-Generation Sequencing." Mol Genet Genomic Med 7.11 (2019): e975.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
