Primary Angiitis of the Central Nervous System (PACNS)
The treatment of primary angiitis of the central nervous system (PACNS) remains challenging due to its rarity, heterogeneous clinical presentation, lack of standardized diagnostic criteria, and limited evidence-based therapeutic options. With our deep expertise in PACNS therapy development, Protheragen is well positioned to provide tailored solutions and comprehensive support to facilitate your journey from PACNS therapy research to commercialization.
Introduction to Primary Angiitis of the Central Nervous System (PACNS)
Primary angiitis of the central nervous system (PACNS) is a rare, idiopathic vasculitis exclusively affecting the brain, spinal cord, and leptomeninges, with an estimated incidence of 2.4 cases per 1,000,000 person-years. It is characterized by focal or diffuse inflammation of small- to medium-sized vessels, leading to ischemic strokes, intracranial hemorrhage, or progressive cognitive decline.
Fig.1 Proposed model of the "Complement Phenotype" of primary angiitis of the central nervous system (PACNS). (Caleigh Mandel-Brehm, et al., 2018)
Pathogenesis of Primary Angiitis of the Central Nervous System (PACNS)
The pathogenesis of primary angiitis of the central nervous system (PACNS) is primarily driven by dysregulated cell-mediated immunity targeting cerebral vasculature, characterized by CD4+ Th1/Th17 lymphocyte infiltration into vessel walls with concomitant release of pro-inflammatory cytokines (IFN-γ, IL-17, TNF-α), leading to granulomatous or lymphocytic vascular inflammation. While the exact trigger remains unknown, genetic predisposition (HLA associations) and possible viral triggers (e.g., VZV) may initiate this aberrant immune response against CNS vasculature.
Therapeutic Development for Primary Angiitis of the Central Nervous System (PACNS)
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Corticosteroids | Broad anti-inflammatory and immunosuppressive effects; inhibits multiple inflammatory pathways | Glucocorticoid receptor (GR) | Approved |
| Cyclophosphamide | Alkylating agent; suppresses immune system by cross-linking DNA, leading to lymphocyte apoptosis | DNA (in rapidly dividing immune cells) | Approved |
| Azathioprine | Purine analog; inhibits DNA synthesis and reduces proliferation of T and B lymphocytes | DNA/RNA synthesis (via conversion to 6-MP) | Approved |
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
Specializing in comprehensive solutions for primary angiitis of the central nervous system (PACNS), Protheragen integrates diagnostic development with cutting-edge in vitro diagnostic (IVD) kits for early disease identification. Our therapeutic development pipeline leverages exclusive disease models, such as physiologically representative blood-brain barrier (BBB) models, to expedite the exploration and authentication of central nervous system (CNS) targeted treatments.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
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Specializing in comprehensive preclinical assessment, Protheragen offers professional pharmacodynamic (PD), pharmacokinetic (PK) and toxicology research services to accelerate the therapeutic development of primary angiitis of the central nervous system (PACNS). If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Caleigh Mandel-Brehm, Hanna Retallack, et al. Evidence for Alternative Complement Cascade Activation in Primary CNS Vasculitis[J]. bioRxiv, 2018.