In case you don’t know Ted is the name of a cute pootch from one of the readers. Like many people they got a Dog during lock down. But could Ted become the solution to MS?
This week I did a post about the name Mouse Doctor and if you remember, we made a comment that people working on cats/dogs and monkeys get special attention when it comes to generating the ire of the anti-vivs (vivisectionists). So some neuros best get their tin hats out, as the abuse is coming their way:-(
So here we go, get Fido into the scanner and lets get their brains out!
Church ME, Ceja G, McGeehan M, Miller MC, Farias P, Sánchez MD, Swain GP, Assenmacher CA, Stopa EG, Vite CH, Bar-Or A, Alvarez JI. Meningeal B Cell Clusters Correlate with Submeningeal Pathology in a Natural Model of Multiple Sclerosis. J Immunol. 2021 Jun 23:ji2000514.
Multiple sclerosis (MS) is an demyelinating disease in which meningeal inflammation correlates with accelerated disease progression. The study of meningeal inflammation in MS has been limited because of constrained access to MS brain/spinal cord specimens and the lack (Just do some reading and you will find! Hope the research wasn’t done as well as their literature review) of experimental models recapitulating progressive MS. Unlike induced models, a spontaneously occurring model would offer a unique opportunity to understand MS immunopathogenesis and provide a compelling framework for translational research (Maybe, but if it has a different aetiological trigger is sends you down a garden path….There was a model of demyelinating disease in cats when they gave them irradiated food when they were pregnant…cue research in pregnant cats…no wonder the guy leading the research got on the hit list. All the anti-vivs had to do was to give him a free ticket to York, a bow and arrow and hope the locals do the rest if the urban myth is to be believed as a throw-back from Braveheart. However I a sure your problem has its origins in the space race and you ate lots of irradiated food as a youngster).
We propose granulomatous meningoencephalomyelitis (GME) as a natural model to study neuropathological aspects of MS. GME is an progressive neuroinflammatory disease of young dogs with a female bias. In the GME cases examined in this study, the meninges displayed focal and disseminated leptomeningeal enhancement on magnetic resonance imaging, which correlated with heavy leptomeningeal lymphocytic infiltration. These leptomeningeal infiltrates resembled tertiary lymphoid organs containing large B cell clusters that included few proliferating Ki67+ cells, plasma cells, follicular dendritic/reticular cells, and germinal center B cell-like cells.…. Although neuroparenchymal perivascular infiltrates contained B cells, they lacked the immune signature of aggregates in the meningeal compartment. Finally, meningeal B cell accumulation correlated significantly with cortical demyelination reflecting neuropathological similarities to MS. Hence, during chronic neuroinflammation, the meningeal microenvironment sustains B cell accumulation that is accompanied by underlying neuroparenchymal injury, indicating GME as a novel, naturally occurring model to study compartmentalized neuroinflammation and the associated pathology thought to contribute to progressive MS.
Granulomatous meningoencephalomyelitis in dogs: A review.O’Neill EJ, Merrett D, Jones B.Ir Vet J. 2005 Feb 1;58(2):86-92 Granulomatous meningoencephalomyelitis (GME) is an inflammatory disease of the central nervous system in dogs that is characterised by focal or disseminated granulomatous lesions within the brain and/or spinal cord, non-suppurative meningitis and perivascular mononuclear cuffing. The aetiology of the disease remains unknown, although an immune-mediated cause is suspected.
So this is spontaneous…so how common is it?….How long are you going to wait for it to occur? This is the problem of using this as a model.
The classical patient is a young to middle-aged small breed dog though any dog of any breed can be affected. What sort of neurologic signs are seen depend totally on what area of the nervous system is involved. Seizures, neck pain, drunken gait, walking in circles, blindness, listlessness, tilted head, facial abnormalities, and weakness can be seen. This does not leave out much in the way of neurologic symptoms. Symptoms can come on acutely or be more chronic. Breeds felt to have a genetic predisposition to GME are Chihuahua, dachshund, Maltese, and miniature poodle.
There are three types of GME: focal (limited to one location in the nervous system); disseminated or multifocal (involving many locations in the nervous system); and ocular (involving the optic nerve/eye). A patient may have more than one type. The disseminated form is the most common.
“A new drug called leflunomide has been released to treat immune-mediated diseases of a type that includes GME. This is a relatively expensive treatment, which has limited use but it remains as a possible alternative to corticosteroid use for dogs that do not tolerate corticosteroid side effects” Leflunomide breaks down to teriflunomide
. So it rather says what happens in MS is an response to something that triggers it and that there different ways to trigger the same phenotype.…unless Doggies get EBV:-)
General Disclaimer: Please note that the opinions expressed here are those of the author and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.