Albinism is a collection of genetic disorders characterized by limited melanin production, leading to a deficiency in pigmentation in the skin and hair, as well as eye abnormalities. At Protheragen, we are developing tailored preclinical approaches targeted toward treat the both cutaneous and ocular aspects of albinism, paying specific attention to the biological mechanisms specific to subtypes and current unmet medical needs.
Introduction to Albinism
Albinism consists of a collection of autosomal recessive disorders most often caused by mutations in genes important for melanin synthesis, such as TYR (tyrosinase), OCA2, and TYRP1. Individuals living with albinism often present with hypopigmentation, photophobia, nystagmus, and vision deficits linked to retinal development peculiarity. The prevalence of albinism is derived from different global populations and ranges by type of albinism; for example, oculocutaneous albinism type 1 (OCA1) derives a global frequency of roughly 1:40,000, however forms more common such as oculocutaneous albinism type 2 (OCA2) and oculocutaneous albinism type 4 (OCA4) respond somewhat populations under environmental influences.
Pathogenesis of Albinism
Albinism is associated with genetic mutations that disrupt melanin biosynthesis that negatively affect the function of enzymes (e.g., TYR) and melanosomal transporters (e.g., OCA2, SLC45A2), resulting in impaired conversion of the amino acid tyrosine to melanin contributing to hypopigmentation of the skin, hair, and eyes. Further, aberrant maturation of melanosomes or failure to properly traffic melanosomes will result in impaired retinal development which can manifest as misrouting of optic nerve fibering and generate nystagmus. Variability in albinism subtypes specifics is attributable to mechanisms that can further define the phenotypic expression, such as TYRP1 stabilizing activity on tyrosinase or GPR143 restricting the motility of anteriorly trafficked melanosomes to the periphery.
Fig.1 The difference between oculocutaneous albinism type 1 and 2. (George
et al., 2022)
Therapeutics Development for Albinism
Melanin Pathway Modulation
- CRISPR-Dependent Gene Activation: dCas9-VPR systems to upregulate MITF or TYRP1 in hypomorphic alleles, achieving 50% melanin rescue in OCA4 iPSC-derived melanocytes.
- Exosome-Based Enzyme Delivery: Tyrosinase-loaded exosomes penetrate epidermal layers, restoring pigmentation in 3D skin equivalents (patent-pending technology).
Neuro-Ophthalmic Interventions
- Optogenetic Retinal Reprogramming: Channelrhodopsin-2 (ChR2) expression in ganglion cells to bypass misrouted optic pathways (proof-of-concept in murine models).
- Stem Cell-Derived RPE Transplants: iPSC-generated retinal pigment epithelium sheets improve visual acuity in albinism-associated foveal hypoplasia.
Our Services
Protheragen offers a great range of capabilities to further the advancement of therapies for albinism. Expert scientist, dermatologists, and geneticists are on hand and leverage cutting edge technologies in their focus on avenues for therapeutic development and disease model development services to support albinism related projects.
Therapeutic Development Platforms for Albinism
Protheragen's albinism therapeutic development platforms leverage gene editing, stem cell-derived melanocyte models, and RNA delivery technologies to target melanin biosynthesis and restore the retinal optic pathway ultimately targeting both cutaneous and ocular aspects of albinism.
Disease Models Development for Albinism
Protheragen further offers a comprehensive suite of preclinical models to advance research associated with albinism, including cutting-edge of 2D cell models, 3D skin models and animal models development all tailored to replicate disease-specific pathologies and accelerate therapeutic development.
| 2D Cell Models & 3D Skin Models |
| Protheragen's preclinical research services for albinism are directed at having your studies yield solid foundations on which to develop therapies. With opportunities to run in vitro studies to engage in experimentation with either 2D cell models, 3D skin models and other optional studies including organoids. |
| Optional Models |
- TYR Knockout Human Melanocytes
|
- Albinism Skin Organoids
- UV Response Chips
|
| Animal models |
| In vivo preclinical studies are also a key part of our services. We utilize, such as genetically engineering models, to test the safety and efficacy of potential therapeutics. These animal models are carefully selected based on their ability to mimic the human condition of albinism. |
| Optional Models |
- Humanized Skin Xenografts
- Zebrafishoca2 −/−
|
- TYR-Knockout Murine Models
|
| Optional Species |
Mice, Rats, Non-human primates, Others |
As a one-stop preclinical research services provider, Protheragen dedicated to advancing therapeutics for rare skin diseases like albinism. Our end-to-end solutions seamlessly from target discovery and disease modeling to in-depth drug safety evaluation and DMPK services. If you are interested in our services, please feel free to contact us.
References
- George, A., et al. "In Vitro Disease Modeling of Oculocutaneous Albinism Type 1 and 2 Using Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium." Stem Cell Reports 17.1 (2022): 173-86.
- Li, C., et al. "Identification and Characterization of Two Novel Noncoding Tyrosinase (Tyr) Gene Variants Leading to Oculocutaneous Albinism Type 1." J Biol Chem 298.5 (2022): 101922.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
