Code of Multiple Sclerosis: New Insights into PPMS, RRMS, and the Promise of Ocrelizumab
Multiple sclerosis (MS) is not a one-size-fits-all disease. While many people are familiar with the term, fewer understand that MS comes in different forms, each with its own challenges and characteristics. A recent scientific review published in Health Science Reports sheds new light on the genetic, immunological, biomarker, and imaging differences between the two major subtypes of MS—primary-progressive (PPMS) and relapsing-remitting (RRMS)—and highlights the emerging role of the drug ocrelizumab in managing tough-to-treat cases.
What is MS—and Why Do Subtypes Matter?
MS is a chronic disease where the immune system mistakenly attacks the central nervous system, damaging the protective myelin sheath around nerves. This leads to a host of symptoms, from vision problems and muscle weakness to cognitive issues.
RRMS (Relapsing-Remitting MS): Makes up ~85% of cases. Characterized by episodes of new or worsening symptoms (relapses) followed by periods of recovery (remission).
PPMS (Primary-Progressive MS): Accounts for 10–15% of MS cases. Unlike RRMS, symptoms steadily worsen over time without clear relapses or remissions.
Understanding these differences is key for tailoring treatment and improving patient outcomes.
Genetics: Clues in Our DNA
Both subtypes have genetic underpinnings, but different ones:
RRMS is strongly linked to immune-related genes like HLA-DRB1, IL-7R, and TNFRSF1A, which influence how immune cells behave.
PPMS shows associations with IL12A, CD58, CHI3L1, and CRYAB. These genes affect myelin repair and neurodegeneration—hallmarks of the progressive form of the disease.
Genetic studies have illuminated how each form may arise and progress, setting the stage for personalized treatments in the future.
Immunology: The Inflammatory Puzzle
RRMS and PPMS both involve immune system dysfunction, but they differ in their cellular culprits:
RRMS: Primarily driven by T cells (especially Th1 and Th17 subtypes) and B cells that create damaging antibodies.
PPMS: Features a more chronic, low-grade inflammation, often with activated microglia and macrophages in the brain and spinal cord.
This difference explains why some immune-modulating treatments work for RRMS but not for PPMS.
Biomarkers: Tracking the Invisible
Scientists are zeroing in on biomarkers—measurable substances in the body that help track disease activity:
Neurofilament light chain (NfL): Elevated in both types, correlates with nerve damage and can be tracked in blood or spinal fluid.
GFAP (Glial fibrillary acidic protein): Especially elevated in PPMS, linked to glial cell damage.
MMP-9, sCD27, and YKL-40: Show promise for distinguishing between MS types and monitoring progression.
These biomarkers could help doctors detect MS earlier, predict flares, and measure response to treatment.
Neuroimaging: The Power of MRI
Advanced MRI techniques are helping distinguish between PPMS and RRMS:
RRMS: Often shows more focal brain lesions, especially in white matter. Gadolinium-enhancing lesions are common, indicating active inflammation.
PPMS: Features spinal cord lesions, gray matter atrophy, and cortical thinning. Imaging reveals widespread damage, not just focal spots.
Emerging tools like diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) allow clinicians to assess subtle changes in myelin and nerve fibers.
Ocrelizumab: A Game-Changer for Tough Cases
Until recently, treatments for PPMS were limited. Enter ocrelizumab, a monoclonal antibody that selectively targets CD20+ B cells—a critical player in the MS immune response.
In RRMS, ocrelizumab reduced relapse rates by nearly 50% and significantly cut new lesion formation.
In PPMS, it slowed disability progression by 24%, making it the first FDA-approved drug for this form of MS.
Ocrelizumab works by depleting B cells while sparing the plasma cells that make protective antibodies—striking a balance between efficacy and safety.
Conclusion: Towards Personalized MS Care
The future of MS treatment lies in precision medicine. As we learn more about the genetics, immune processes, and imaging features of MS subtypes, we can tailor treatments more effectively. Ocrelizumab is a promising step in that direction, especially for patients who previously had few options.
Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.
References:
Prajjwal, P., Marsool, M. D. M., Asharaf, S., Inban, P., Gadam, S., Yadav, R., ... & Amir, O. (2023). Comparison of recent updates in genetics, immunology, biomarkers, and neuroimaging of primary‐progressive and relapsing‐remitting multiple sclerosis and the role of ocrelizumab in the management of their refractory cases. Health Science Reports, 6(7), e1422.
