How do you get rid of CNS inflammation has been a question and it was recently posed by ProfK one or three times with cladribine. Cladribine gets into the CNS at active levels and so the question has been can we get rid of oligoclonal bands…The Makers of CLAD funded two trials and the answer they came up with was yes because cladribine reduced the number of oligoclonal bands…We did the same experiment independently of pharma and we concluded that they were still there and it is perhaps not surprising as the antibody producing cells do not express the target for cladribine. So it couldn’t directly kill the antibody producing cells. However it could kill the precursors for the antibody producing cell and so reduce them in the CNS and it may also remove the cells that support the survival of the antibody producing cells, however we also thought that the data perhaps suggests that cladribine could kill the short-lived antibody producing cells leaving the long-lived plasam cells to maintain the spinal fluid as positive for oligoclonal bands. So I was interested to see a paper saying
“Jendretzky KF, Wurster U, Konen FF, Döring K, Friedrich JF, Nay S, Möhn N, Grote-Levi L, Hümmert MW, Sühs KW, Schwenkenbecher P, Gingele S, Skripuletz T. Assessing the value of oligoclonal band count in multiple sclerosis: insights from a large cohort analysis. Front Neurol. 2026; 17:1719470”
They say “Cerebrospinal fluid (CSF) specific oligoclonal bands (OCB) are a key diagnostic marker in multiple sclerosis (MS). Recent studies suggest that OCB reduction may reflect treatment efficacy and propose it as a potential endpoint in trials with chimeric antigen receptor (CAR) T-cell therapy. However, the prognostic value of baseline OCB count remains unclear. This study analyzed data from 454 persons (314 had MS, 140 clinically isolated syndrome). OCB analysis was performed by isoelectric focusing in polyacrylamide gel, followed by silver staining. The correlation of the number of OCBs with clinical and paraclinical parameters as well as follow-up outcomes was evaluated. Our results showed that in OCB positive persons with MS, the median number of CSF specific bands was 19. No significant correlation was found between OCB count and age, sex, initial EDSS, or MRI lesion load. OCB count also did not predict relapse risk or EDSS progression. However, strong correlations were observed with intrathecal synthesis of IgG and kappa free light chains. Therefore, our conclusion is that OCB count does not reflect clinical disease activity at diagnosis nor predict clinical progression within the observed median follow-up period of 9 months. Whether a decrease in OCB count indicates reduced humoral immune response in the CNS under certain therapies remains unclear and requires further prospective studies.
So there was not alot of insight.
They did a study with natalizumab and anti-CD20 and they conclude OCB remained positive in 10/11 persons treated with natalizumab (median treatment duration: 25 months, IQR 8.5–50.75) and in 9/10 persons treated with anti-CD20 antibodies (median 13 months, IQR 6.25–26.25)
So this is just like cladribine and I hate to say it just like CD19 CART-T therapy and so it says the therapies are not targeting long lived antibody secreting cells in the CNS. Natalizumab does not get or work in the CNS but previous studies have said it can reduce the number of bands. Likewise anti-CD20 does not target short or long lived antibody secreting cells and again is 99.9% excluded from the CNS. Therre was a suggetion that some people lost the number of bands ,but they didn’t look at every of the 19 positive people. Working out what the bands and where they come from is key. BCMA-CAR-T should have the potential to get into the CNS to kill plasma cells but does it? Does it get in the bone marrow and wipe out all of your childhood vaccine responses which it should be doing if it is wiping out B cell responses in the brain. Maybe I will write a review about the source of oligoclonal bands it is important when you are thinking about the number of bands
COI: None
Disclaimer. My views alone…as ever
Source: multiple-sclerosis-research.org