Unchecked Lymphocyte Trafficking Across the Blood-Brain Barrier
Placeholder: autoreactive lymphocytes cross the BBB and attack myelin.
- 100%: CNS infiltration (baseline) (relative, no therapy)
- 100: Circulating lymphocytes (relative baseline units)
- ~0.4–0.6: Annual relapse rate (untreated) (placeholder reference)
- high: Myelin attack events (placeholder qualitative)
Why lymphocytes reach the CNS
Placeholder: activation, adhesion, transmigration steps summarized briefly.
Consequence of unchecked infiltration
Placeholder: demyelination and relapse risk without intervention.
Three Drug Classes, Three Distinct Points of Intervention
Placeholder: pick ocrelizumab, natalizumab, or fingolimod to compare.
- CD20: Ocrelizumab target (B-lymphocyte surface marker)
- α4-integrin: Natalizumab target (adhesion receptor)
- S1P1: Fingolimod target (sphingosine-1-phosphate receptor)
- IV / IV / oral: Route (placeholder dosing summary)
Depletion vs. blockade vs. retention
Placeholder: each drug intercepts the attack at a different stage.
Choosing between mechanisms
Placeholder: efficacy, risk, and monitoring trade-offs briefly noted.
How Each Therapy Physically Interrupts the Attack
Placeholder: antibody depletion, integrin blockade, or lymph-node trapping.
- B-cell depletion: Ocrelizumab action (anti-CD20 antibody binding)
- Adhesion blockade: Natalizumab action (α4-integrin / VCAM-1 blocked)
- Lymph node retention: Fingolimod action (S1P1 internalization traps cells)
- weeks–months: Onset of action (placeholder timeframe)
Ocrelizumab — anti-CD20 depletion
Placeholder: antibody binds CD20, marks B-cells for clearance.
Natalizumab — integrin blockade
Placeholder: blocks adhesion so cells cannot cross the BBB wall.
Fingolimod — S1P receptor modulation
Placeholder: lymphocytes stay sequestered inside lymph nodes.
CNS Infiltration Falls as Each Mechanism Takes Hold
Placeholder: three routes converge on the same outcome — quieter CNS.
- ~82%: Ocrelizumab infiltration cut (placeholder max effect)
- ~96%: Natalizumab infiltration cut (placeholder max effect)
- ~78%: Fingolimod infiltration cut (placeholder max effect)
- ~6–12 mo: Time to plateau (placeholder curve shape)
Infiltration curves over therapy duration
Placeholder: effect builds over months, not instantly.
Myelin attack quiets accordingly
Placeholder: fewer lymphocytes in CNS, fewer attack events.
Relapse Reduction Achieved, at Different Monitoring Costs
Placeholder: comparable efficacy, divergent safety monitoring needs.
- ~47%: Ocrelizumab relapse reduction (placeholder trial figure)
- ~68%: Natalizumab relapse reduction (placeholder trial figure)
- ~54%: Fingolimod relapse reduction (placeholder trial figure)
- varies: Key risks (infection / PML / cardiac-ocular)
Efficacy compared across mechanisms
Placeholder: natalizumab highest, ocrelizumab and fingolimod close behind.
Distinct side-effect and monitoring profiles
Placeholder: infusion/infection, PML, or cardiac/ocular monitoring.
Drug-specific monitoring at a glance