Mouse EAEers currently use myelin oligodendrocyte glycoprotein to induce disease, with which to study MS.
However, do people with MS respond to this protein
Papp V, Langkilde AR, Blinkenberg M, Schreiber K, Jensen PEH, Sellebjerg F. Clinical utility of anti-MOG antibody testing in a Danish cohort. Mult Scler Relat Disord. 2018 Sep 11;26:61-67. doi: 10.1016/j.msard.2018.09.010. [Epub ahead of print]
BACKGROUND: Anti-myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) can be found in different immune-mediated inflammatory CNS disorders. The full range of clinical manifestations may not have been fully discovered yet.
METHODS:In a cross-sectional study 184 adults (age ≥ 16) were tested for anti-MOG antibody (Ab) with a cell-based assay. To define the relevant target population for anti-MOG antibody testing in a neurology clinic, we divided the entire study population based on the presenting symptoms and classified cases followed for multiple sclerosis (MS) according to the clinical features and response to disease-modifying therapy.
RESULTS:We identified eight (4.4%) MOG-Ab positive cases in the whole cohort. All eight cases had first manifestations suggestive of neuromyelitis optica spectrum disorder (NMOSD), but had highly variable disease courses and responses to therapy. This included a patient with chronic relapsing inflammatory optic neuropathy (CRION) responding only to therapy with infliximab. Four (3%) out of 134 cases followed for MS who tested positive for anti-MOG Ab showed atypical features and had poor response to therapy.
CONCLUSION:A broad range of clinical and radiological features of anti-MOG associated disorder was observed in a single centre. MOG-Ab testing should be considered in patients with an NMOSD phenotype and in MS patients presenting atypical features. The potential use of infliximab therapy for MOG-Ab disease should be further investigate
The simple answer is not many, as can be seen above.
So first it was myelin basic protein and now it is MOG that the modellers think is important in MS, when both have been discredited. MBP could have been thrown away with 5 minutes of thought (I is not CNS restricted like MS, and there is little disease related extra activity) people with disease but it took countless trials. It was investigated because it was water soluble and easy for the T cell immunologists to make and was the mainstay until recombinant technology to make proteins and peptides came along. Proteolipid protein which is the major CNS myelin protein still does not get a look in because it is like brick dust and doesn’t dissolve in water so not great for the T cell immunologists unless you have a water soluble epitope. So myelin oligodendrocyte found favour, particularly because it was on the outside of the nerve and could be targeted by antibodies and most importantly it was the protein that best induced EAE in transgenic mice, which are on the C57BL/6 mouse background. MOG35-55 was found to induce disease and the rest we say is history.
This history shows that MOG35-55 is not the main pathogenic epitope in MOG in C57BL/6 and that few humans with MS respond to MOG as this study shows. Indeed I have a HLA-DR type that doesn’t. yipee.
Furthermore, if people may antibodies to, it the disease is more neuromyelitis optica like. Therefore the protein has little validity as a target antigen MS.
I am not aware of MOG trials yet, which is a good thing.
However it probably does not matter if the questions you are asking
are not about MOG the autoantigen, you can use the mice as tools.
Maybe we should all watch this video before using animals (CLICK HERE)
The 3Rs. Their definition, application and importance to your work from NC3Rs on Vimeo.