Monilethrix is an uncommon genetic hair disorder where the hair shaft is weak or has a beaded structure due to mutations in hair keratin genes, which causes hair breakage and hair loss. Protheragen provides complete preclinical service of drug and therapy design which helps in the translational research of Monilethrix and subsequently aids in the therapeutic of the disorder.
Introduction to Monilethrix
Monilethrix hair is described as fragile and beaded in appearance. The disorder also comes with alopecia or partial hair loss. In most cases, the dominant gene in monilethrix has a single trait with different forms along with an autosomal recessive gene is believed to be responsible for the disorder. Mutations in hair keratin genes, most notably KRT81, KRT83, and KRT86 are believed to cause Monilethrix. Due to the lack of sufficient data and research, the number of reported cases of Monilethrix is rare. They are known to exist all around the world, regardless of ethnicity.
Fig.1 Scanning electron microscopy, dermoscopy, and histopathology examination of the patient. (C. Zhou
et al., 2022)
Pathogenesis of Monilethrix
Monilethrix is a hereditary hair shaft disorder caused by mutations in the KRT81, KRT83, or KRT86 genes, which encode type II hair cortex keratins essential for hair structure and strength. These mutations lead to defective keratin proteins and abnormal keratin intermediate filament formation within hair follicle cells. As a result, the hair shaft develops periodic constrictions and dilations, giving it a characteristic beaded appearance and making the hair prone to breakage due to structural weakness.
Fig.2 Schematic representation of the human DSGs arrangement on chromosome 18q12.2. (C. Zhou
et al., 2022)
Therapeutics Development for Monilethrix
Gene Therapy and Genetic Approaches
Advances in gene editing technologies offer therapeutic possibilities for Monilethrix by correcting mutations in key genes KRT81, KRT83, or KRT86 to restore normal keratin production. Ex vivo gene therapy involves modifying keratinocyte stem cells from the patient for transplantation back to the scalp. Antisense oligonucleotides may also alter the expression or splicing of mutant keratin genes.
Small Molecule and Topical Therapies
Research is focused on discovering agents that improve hair shaft structure or compensate for defective keratins. Retinoids like acitretin, which promote keratinocyte differentiation, may affect hair and nail growth. While topical agents like minoxidil are used to aid hair growth, their effectiveness in Monilethrix is questionable. Other small molecules aim to increase expression of compensatory keratins or stabilize hair shaft structure.
Stem Cell and Regenerative Therapies
Researchers are exploring the use of stem cells to provide new hair follicles for people with Monilethrix. This includes hair follicle stem cell transplantation, where the patient's own or donor stem cells are cultured and implanted to enable normal hair growth. There is also work on tissue engineering to develop bioengineered hair follicles for transplantation.
Our Services
Protheragen integrates multidisciplinary research on monilethrix, including dermatology, genetics, and molecular biology, managing keratin gene pathologies under collaborative programs focused on therapeutic development and disease model development for your research project.
Therapeutic Development Platforms for Monilethrix
Protheragen works on small molecule modulators to restore normal hair shaft formation in patients with monilethrix by targeting disrupted keratinization processes. They are developing gene-targeted strategies to correct mutations in hair keratin genes, such as KRT81, KRT83, and KRT86, to promote healthy hair growth.
Disease Model Development for Monilethrix
Protheragen provides a comprehensive preclinical portfolio for monilethrix comprising 2D cell models, 3D skin models and animal models all developed to enact relevant disease pathologies and enable therapy development.
| 2D Cell Models & 3D Skin Models |
| Protheragen utilizes 2D cell models and advanced 3D skin models to study the molecular pathways of monilethrix. This allows in vitro testing of multiple candidate drugs on the skin for safety and efficacy evaluation during the preclinical phase of drug development. |
| Optional Models |
- Human Keratinocyte Monolayer Cultures
- Hair Follicle Organoid Models
|
- 3D Skin Equivalents
- Spheroid Culture Models
|
| Animal models |
| Protheragen's preclinical in vivo studies employ animal models, including genetically engineering models tailored to monilethrix, to evaluate therapeutic safety and efficacy while ensuring biological relevance to disease mechanisms. |
| Optional Models |
- Krt81 Knock-In Mouse Model
- Krt83 Knock-In Mouse Model
|
- Krt86 Knockout Mouse Model
- Inducible Krt81 Mutation Mouse Model
|
| Optional Species |
Mice, Rats, Non-human primates, Others |
As a specialized preclinical research partner, Protheragen supports therapeutic innovation for rare skin diseases like monilethrix. Our end-to-end services include target discovery, disease modeling, drug safety evaluation and DMPK services. If you are interested in our services, please feel free to contact us.
References
- Binamer, Y., and M. A. Chisti. "Kindler's Syndrome with Recurrent Neutropenia: Report of Two Cases from Saudi Arabia." J Pediatr Genet 12.1 (2023): 69-72.
- Zhan, J., et al. "Monilethrix Protein Kindlin-1 Is Mainly Expressed in Adult Tissues Originating from Ectoderm/Endoderm." Sci China Life Sci 58.5 (2015): 432-41.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
