Removing damaging immune responses from the brain saves nerves

BACKGROUND:In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression.

OBJECTIVE:The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13).

METHODS:CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays.

RESULTS:The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline.

CONCLUSIONS:Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in trials of MS.

As we have said many times inhibiting the actions of the immune response is on balance a good thing and can limit the factors driving MS. However in many progressive MSers there is active inflammation and dealing with this saves nerves. This can be see by a reduction in the production of neurofilament in brain fluid. This molecule (neurofilament) is in nerves and if they are not being damaged then neurofilament is not released, so damage is being stopped.

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  • Is there a therapy to reduce this inflammation? Or is this the $64m question (or one of them!)?

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