Multiple sclerosis (MS) develops exclusively in humans. Non-human primates are resistant against MS, although they are highly susceptible to the MS animal model, experimental autoimmune encephalomyelitis (EAE). Unravelling of the cause(s) underlying this discrepancy is highly relevant as insights might be gained into the elusive event(s) that trigger(s) MS. A well-established difference between the human primate (Homo sapiens) and non-human primates is that humans are unable to synthesize the sialic acid N-glycolylneuraminic acid (Neu5Gc).
We propose the concept that long-term ingestion by human primates of the foreign Neu5Gc, via red meat consumption, is an ignored environmental risk factor for MS. Conceptually, incorporation of dietary Neu5Gc into vital regions of the central nervous system, such as the blood-brain barrier (BBB) and the axon-myelin unit, creates targets for binding of de novo synthesized heterophilic anti-NeuGc antibodies. Binding of the antibodies can cause BBB leakage and destabilization of the axon-myelin coupling. The ensuing cytodegeneration and release of self-antigens could be a start of the characteristic pathological features of MS.
Professor Hart is clearly going out on a limb here, none of his colleagues have deigned to join him in co-authoring this manuscript. However, I like to form my own opinions and have come to the conclusion that another theory wouldn’t go amiss in the long list of plausible explanations for MS.
Hart raises a valid question, which is why MS develops spontaneously in humans (which he calls human primates), but not in related non-human primate (NHP), such as the chimpanzee? Now chimps share a genome that has >98% genetic similarity to us – ergo are very similar to us in their immune system, and breathe the air that we breathe, and live in the temperate climes linked to high rates of MS. Now NHPs don’t smoke, but they do develop a chronic latent infection with EBV-like viruses and their hairy pigmented skin is not conducive to vitamin D production – and yet no MS.
So what does Hart suggest? He proposes a new candidate, Neu5Gc (N-glycolyneuraminic acid) as the culprit in triggering MS. Neu5Gc is found at the end of most glycoproteins in our bodies, but is absent in the CNS, where its production is supressed and its expression here may be detrimental. Humans unlike NHPs cannot synthesise Neu5Gc on their own; a change which took place around 3 million years ago in the hominoid lineage. But when human tissues are studied, it is present. The main source for this, therefore is in the diet, in particular from red meat (beef, pork, lamb). He further suggests that there is strangely an overlap between the global MS risk and areas with high intake of meat from livestock as part of their daily diet.
Hart may have a point, but can we prove this? By probability alone there is a 50/50 chance that the answer to this question is a YES.