Niemann-Pick Disease (NP)
Niemann-Pick disease (NP) is a group of inherited lysosomal storage disorders characterized by pathological accumulation of sphingolipids and cholesterol in multiple organs. To address the complexities of managing NP, Protheragen has committed resources to cutting-edge technologies and expert professionals focused on pioneering therapeutic solutions. Our comprehensive support services will significantly streamline your path from drug candidate development to market entry.
Introduction to Niemann-Pick Disease (NP)
Niemann-Pick disease (NP) represents a spectrum of autosomal recessive lysosomal storage disorders characterized by pathological accumulation of sphingolipids (particularly sphingomyelin) and cholesterol in multiple organ systems. The disease is classified into three major subtypes with distinct genetic and clinical profiles:
| Subtypes | Gene Defect | Deficient Enzyme/Protein | Primary Accumulated Lipid | Key Clinical Features |
| Type A (NPD-A) | SMPD1 mutations | Acid sphingomyelinase (ASM) | Sphingomyelin | Infantile neurodegeneration, hepatosplenomegaly (death by age 3) |
| Type B (NPD-B) | SMPD1 mutations | Partial ASM deficiency | Sphingomyelin | Chronic visceral involvement (lung/liver disease), survival to adulthood |
| Type C (NPC) | NPC1 (95%) or NPC2 (5%) mutations | NPC1/NPC2 cholesterol transporters | Unesterified cholesterol | Ataxia, vertical gaze palsy and systemic manifestations |
Pathogenesis of Niemann-Pick Disease (NP)
Niemann-Pick diseases (NP) are caused by genetic defects disrupting lysosomal lipid metabolism: in NPD-A/B, SMPD1 mutations cause acid sphingomyelinase deficiency, leading to toxic sphingomyelin accumulation in viscera and neurons; in NPC, NPC1/NPC2 mutations impair cholesterol trafficking, resulting in lysosomal cholesterol sequestration and secondary neurodegeneration. Both pathways trigger organ dysfunction (liver/spleen enlargement) and CNS deterioration through lipid-induced oxidative stress and cell death.
Fig.1 A proposed model for the pathogenesis of Niemann-Pick disease (NP) type B. (Canonico B, et al., 2016)
Therapeutic Development for Niemann-Pick Disease (NP)
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Aqneursa | Recombinant acid sphingomyelinase (ASM) with enhanced blood-brain barrier penetration | Acid sphingomyelinase | Phase I/II |
| Miplyffa | NPC1 protein stabilizer that restores cholesterol trafficking | NPC1 cholesterol transporter | Approved |
| Lovastatin | HMG-CoA reductase inhibitor that reduces cholesterol synthesis | HMG-CoA reductase | Phase III |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
As a preclinical research service provider for Niemann-Pick diseases (NP), Protheragen provides end-to-end diagnostic and therapeutic development solutions. We excel in building physiologically relevant models, including in vitro models, animal models, and specialized blood-brain barrier (BBB) models, to enable comprehensive biomarker discovery, target validation, and CNS drug efficacy optimization.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- Npc1nih Mouse Model
- Npc1spm Mouse Model
- Npc1pf Mouse Model
- Npc1nmf164 Mouse Model
- Npc1a57A Drosophila Model
- Other Models
At Protheragen, we offer comprehensive pharmacodynamic (PD), pharmacokinetic (PK), and toxicology research services to support the development and regulatory approval of potential therapies for Niemann-Pick diseases (NP). If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Canonico B, Cesarini E, Salucci S, et al. Defective autophagy, mitochondrial clearance and lipophagy in niemann-pick type B lymphocytes[J]. PloS one, 2016, 11(10): e0165780.