Niemann-Pick Disease
Niemann-Pick disease is a heterogeneous group of rare inherited metabolic disorders characterized by the abnormal buildup of lipids, such as sphingomyelin or cholesterol, in different tissues and organs of the body. Our company stands at the forefront of innovation in the realm of rare diseases, including Niemann-Pick disease, by offering a comprehensive suite of resources and services tailored to empower researchers.
Introduction to Niemann-Pick Disease
The spectrum of Niemann-Pick disease encompasses several subtypes, including Type A, B, C, and E, each presenting unique manifestations and genetic underpinnings. Type A and Type B, the more prevalent forms of the disease, exhibit an incidence rate of 1 in 250,000 individuals, while Type C affects approximately 1 in 150,000 persons. On the other hand, Type E represents a less common variant that typically emerges in adulthood, adding further complexity to the disease landscape.
Fig.1 Summary of how NPC1 defects occur in different diseases. (Platt F. M., 2023)Pathogenesis of Niemann-Pick Disease
At the core of Niemann-Pick disease pathogenesis are genetic mutations affecting critical lipid metabolism genes, leading to aberrant lipid accumulation within the cell. In Type A and Type B Niemann-Pick disease, disruptions in the SMPD1 gene encoding acid sphingomyelinase (ASM) result in the intracellular buildup of sphingomyelin, whereas mutations in the NPC1 or NPC2 genes drive cholesterol accumulation within lysosomes in Type C Niemann-Pick disease. These lipid imbalances disrupt cellular functions and trigger tissue damage, particularly impacting vital organs like the liver, spleen, and brain in severe cases.
Fig.2 Molecular pathogenetic mechanisms in Niemann-Pick disease. (Tirelli, C., et al., 2024)
Biomarkers of Niemann-Pick Disease
Biomarkers serve as indispensable tools in unraveling the underlying mechanisms of Niemann-Pick disease, aiding in prompt diagnosis, disease monitoring, and evaluation of therapy responses. Here are some commonly studied biomarkers associated with Niemann-Pick disease:
- Chitotriosidase
- Oxysterols
- Cholenoic acid sulfates
- Cholenoic acids
- Sphingosylphosphorylcholine
- Glycosylsphingosine
- N-Palmitoyl-O-phosphocholine-serine
- Others
Therapeutics Development of Niemann-Pick Disease
| Types | Drug Names | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|---|
| Small molecule drug | Miglostat | Inhibit the central nervous system progression | Glucosylceramide synthase | Approved |
| HPBCD | A cyclodextrin derivative with cholesterol inclusion activity | Cholesterol | Phase II trials | |
| Vorinostat | Reduce the accumulation of lipids in the lysosomes | HDAC | Phase I/II trials | |
| Arimoclomol | Amplifies HSP gene expression and facilitates the induction of HSPs | HSP | Phase II/III trials | |
| Gene therapy | Npc1 cDNA transgene | Production of a functional Npc1 protein | Npc1 | Preclinical research |
Our Services
From cutting-edge research tools and resources with our animal model and therapeutic development platform to offering expert consultation services and collaborative opportunities, our company ensures that researchers have all the essential support and expertise they require to advance their work effectively.
Therapeutics Development Platforms
Animal Models of Niemann-Pick Disease
Animal models play a crucial role in studying diseases like Niemann-Pick disease to understand their pathogenesis and develop potential therapeutics. Our company provides various animal models to empower scientists to gain novel insights into rare diseases like Niemann-Pick disease and drive progress toward improved diagnostics and therapeutics.
| Genetically Engineered Models | ||
| The models use genetic engineering techniques such as CRISPR/Cas9 to introduce mutations in key genes associated with Niemann-Pick disease, such as the NPC1 or NPC2 genes, to replicate the genetic defects seen in affected individuals. | ||
| Optional Models |
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| Optional Species | Mice, Rats, Zebrafish, Non-Human Primates, Others | |
Specializing in rare diseases, we provide a comprehensive array of one-stop services including pharmacokinetic studies and drug safety evaluations, uniquely designed to address the diverse and intricate needs of researchers in Niemann-Pick disease. If you are interested in our service, please don't hesitate to contact us.
References
- Platt, Frances M. "The expanding boundaries of sphingolipid lysosomal storage diseases; insights from Niemann-Pick disease type C." Biochemical Society transactions 51.5 (2023): 1777-1787.
- Tirelli, Claudio et al. "The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann-Pick Disease: A Comprehensive Review." Biomolecules 14.2 (2024): 211.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.