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Project Description

Please note that we are not a pharmacy or clinic, so we are unable to see patients and do not offer diagnostic and treatment services for individuals.

Cartilage-Hair Hypoplasia Syndrome (CHH)

Cartilage-Hair Hypoplasia (CHH) Syndrome is a rare genetic disorder identified by skeletal dysplasia, immune deficiency, and fine sparse hair. Individuals with CHH require new and innovative diagnostics and therapeutics. Protheragen provides end-to-end preclinical drug and therapeutic development services for CHH, accelerating advancement of your research project.

Overview of Cartilage-Hair Hypoplasia

Cartilage-Hair Hypoplasia (CHH), is a rare autosomal recessive disorder caused by pathogenic variants in the RMRP gene that encodes the RNA component of the mitochondrial RNA-processing endoribonuclease. The incidence of CHH in the world is estimated to range between 1:20,000 to 1:30,000, with some founder populations such as the Finnish and Amish having much higher incidence rates. Recent publications have highlighted the molecular heterogeneity of CHH and that pathogenic variants in RMRP lead to impaired ribosomal RNA processing, cell cycle regulation, and impaired mitochondrial function.

The human mitochondrial RNA-processing ribonuclease comprises ten protein subunits and RMRP's RNA structure.

Fig.1 The structure of human mitochondrial RNA-processing ribonuclease, showing ten protein subunits and the secondary structure of the RNA component RMRP. (Vakkilainen, Taskinen and Makitie, 2020)

Biomarkers Development for Cartilage-Hair Hypoplasia

Biomarker Discovery: Advances in CHH biomarker research in the last few years have identified novel metabolic and molecular signatures associated with the disease pathology. For example, it has been shown that individuals with CHH have elevated serum lactate and pyruvate levels which are a reliable biomarker of mitochondrial dysfunction caused by RMRP mutations.

Rapid Genetic Testing: New tools are being developed that facilitate greater than 99.9% certainty in the CHH genetic diagnosis faster than previously known. Third generation sequencing has been able to detect non-coding RMRP variants, such as promoter mutations that were not able to be detected by traditional NGS.

Therapeutics Development for Cartilage-Hair Hypoplasia

mRNA Therapeutics

mRNA Therapeutics: LNP-encapsulated RMRP mRNA has been shown to restore ribosomal rRNA processing in vitro, without the risks of genomic integration. The development of tissue-specific LNPs that target cartilage and bone marrow is in progress. Systemic delivery of mRNA pre-clinical studies demonstrated a reduced skeletal phenotype in RMRP CHH mouse models.

Stem Cell Therapy

Stem Cell Therapy: Allogeneic HSCT remains of utmost importance for correcting the immunodeficiency, while the engineered thymic organoids will further enhance post-HSCT T-cell maturation. We have shown that iPSCs can be differentiated into chondrocytes to model and repair skeletal dysplasia, demonstrating future therapy potential in murine trials.

Our Services

Protheragen offers a full range of services to accelerate the advancement of therapies for cartilage-hair hypoplasia. Our expert scientific team of scientists, dermatologists, and geneticists use cutting-edge preclinical technologies, with the focused therapeutic development and disease model development services to support your research projects.

Therapeutic Development Platforms for Cartilage-Hair Hypoplasia

Disease Models Development for Cartilage-Hair Hypoplasia

Protheragen offers custom in vitro (2D Cell Models and 3D Skin Models) to study CHH-specific molecular pathologies in cellular differentiation defects and tissue dysregulation. Our animal models likewise recapitulate critical disease phenotypes such as skeletal dysplasia and immune dysfunction, supporting robust preclinical validation.

2D Cell Models & 3D Skin Models

Patient-Derived Chondrocytes
RMRP-Knockout Induced Pluripotent Stem Cells
3D Chondrogenic Organoid Systems

Animal Models Development

RMRP Conditional Knockout Mice
Zebrafish rmrp Mutant Models
Humanized Immune Dysfunction Models

Utilizing gene-edited disease models, multi-omics analytics and high-throughput screening, we deliver actionable insights to de-risk your therapeutic development pipeline. Please contact us to discuss how our end-to-end preclinical expertise can enhance your cartilage-hair hypoplasia project.

References

Rozas-Munoz, E., et al. "Extensive and Deep Granulomatous Ulcers as an Atypical Manifestation of Cartilage-Hair Hypoplasia Syndrome: A Diagnostic and Therapeutic Challenge." Australas J Dermatol 65.3 (2024): 272-75.
Vakkilainen, S., M. Taskinen, and O. Makitie. "Immunodeficiency in Cartilage-Hair Hypoplasia: Pathogenesis, Clinical Course and Management." Scand J Immunol 92.4 (2020): e12913.

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