Chanarin-Dorfman syndrome (CDS) is an extremely rare disorder that is inherited in an autosomal recessive manner. Protheragen focuses on precision preclinical strategies targeting the root causes of CDS, from lipid metabolic dysfunction to multi-organ pathology, with the goal of accelerating therapies for this underserved condition.
Introduction to Chanarin-Dorfman Syndrome
Chanarin-Dorfman Syndrome (CDS): A rare autosomal recessive disorder characterized by systemic accumulation of neutral lipids due to mutations in the ABHD5/CGI-58 gene, which disrupts lipid metabolism. Clinical features include ichthyosis, hepatomegaly, a myopathy, and varied neurological manifestations. The overall global prevalence is estimated to be <1:1,000,000. CDS requires targeted therapeutic strategies for multisystemic pathophysiology.
Fig.1 Structure of ABHD5/CGI-58 gene and its reported mutations in CDS patients. (Cakmak and Bagci, 2021)
Pathogenesis of Chanarin-Dorfman Syndrome
CDS is caused by loss-of-function mutations in ABHD5, which regulates adipose triglyceride lipase (ATGL) responsible for the breakdown of lipid droplets. A non-functioning ABHD5 leads to impaired lipolysis resulting in the intra-tissue accumulation of lipid in the skin, liver, muscle, and other tissues. Secondary pathophysiology is attributable to mitochondrial dysfunction, oxidative stress, and inflammation, leading to progressive multi-organ damage. Disease-modifying genetic variants (e.g., PNPLA2 variants) may contribute to differences in phenotypic severity, including hepatic fibrosis or neuromuscular degeneration.
Therapeutics Development for Chanarin-Dorfman Syndrome
Gene Therapy & Enzyme Replacement
- AAV-Mediated ABHD5 Delivery: AAV8 vectors restored lipid metabolism in ABHD5-knockout murine models with significant decreases in hepatic steatosis and skin pathology.
- Recombinant ATGL Protein: Identified engineered ATGL variants with enhanced stability have previously indicated some promise in restoring almost full patient fibroblast lipolysis.
Small Molecule Drugs
- Lipid Metabolism Modulators: PPAR-α agonists (e.g., fenofibrate) improve lipid clearance, mitochondrial function in preclinical models.
- Autophagy Enhancers: Rapamycin analogs reduce lipid accumulation by driving autophagic flux in CDS obtained cell lines.
Our Services
Protheragen offers a full range of services to accelerate therapeutics for chanarin-dorfman syndrome. Our team of expert scientists, dermatologists, and geneticists leverage their expertise with advanced technologies to your benefit with area based therapeutic development and disease model development services for your projects.
Therapeutic Development Platforms for Chanarin-Dorfman Syndrome
At Protheragen, we deliver an integrated end-to-end solution across small molecule, gene therapy, cell therapy and biologic platforms for broad reading applications addressing ABHD5 driven lipid metabolic dysfunction in chanarin-dorfman syndrome.
Disease Models Development for Chanarin-Dorfman Syndrome
Protheragen offers a wide and comprehensive suite of preclinical models to move chanarin-dorf man syndrome research forward, including cutting-edge 2D cell models, 3D skin models and animal models development specifically customized to replicate disease-specific pathologies and to move therapeutics forward.
| 2D Cell Models & 3D Skin Models |
| Protheragen's preclinical models research services for chanarin-dorfman syndrome are built-designed as a solid foundation for the development effective therapies. We perform in vitro studies using 2D cell models and 3D skin models to detect and study the molecular mechanisms of chanarin-dorfman syndrome. |
| Optional Models |
- Patient-Derived Fibroblasts
- ABHD5-Knockout Hepatocyte Lines
- Immortalized Keratinocytes
|
- Skin-Liver Co-Culture Organoids
- Adipose-Liver Microphysiological Systems
|
| Animal models |
| In vivo preclinical studies are also a meaningful part of our services. We will use, such as genetically engineering models, to test the safety and efficacy of proposed therapeutics. These animal models are carefully selected based on their ability to mimic the human condition of chanarin-dorfman syndrome. |
| Optional Models |
- Abhd5-/- Mice
- Alb-Cre; Abhd5flox/flox Mice
|
|
| Optional Species |
Mice, Rats, Non-human primates, Others |
As a one-stop preclinical research services provider, Protheragen supports the development of therapies for rare conditions affecting skin, such as chanarin-dorfman syndrome. We offer end-to-end solutions through our team of scientists ranging from target discovery, disease modeling, through drug safety evaluation and DMPK services. If you are interested in our services, please feel free to contact us.
References
- Cakmak, E., and G. Bagci. "Chanarin-Dorfman Syndrome: A Comprehensive Review." Liver Int 41.5 (2021): 905-14.
- Durmazer, E., et al. "Chanarin-Dorfman Syndrome Diagnosed at the Stage of Liver Transplantation: A Rare Lipid Storage Disease." J Clin Lipidol 18.1 (2024): e125-e28.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
