Could a vaccine cure MS?

Ian Cook unearths some interesting research with some serious pharmaceutical funding behind it

One approach to treating multiple sclerosis (MS) is often overlooked but is surprisingly simple, some might say simplistic. You simply focus on the auto-immunity linked to MS and develop a body tolerance to what is causing it. If this works the body stops attacking itself, MS goes away and we are all cured, hoorah.

Well, that’s the theory and it’s been around for years. In practical terms researchers develop something called an ‘inverse vaccine’. Unlike traditional vaccines that give the immune system a glimpse of the problematic substance to fight off, inverse vaccines introduce the problematic substance through a process that encourages the immune system to tolerate or simply ignore it. In MS, for example, this problematic substance would be myelin, or something in myelin and our bodies learn to ‘tolerate’ it and not attack it.

Food allergies

This theory of exposing the body to the problematic substance has recently been tried out in food allergies with some success. In the US researchers have been working on an immunotherapy to tackle peanut allergy. Positive results were published in the Lancet in 2022. Based on this research it seems conceivable that immune system tolerance can be established in the human body where the problematic substance or auto-antigen is identified as it has been in food allergy.

But there are major challenges in extending this idea to auto-immune diseases or immune mediated diseases such as MS. While MS is seen as a de-myelinating disease, with myelin being the obvious auto-antigen, the unanswered question is – what substance or substances in myelin causes auto-immunity? The obvious candidate is myelin basic protein (MBP) as this is present in both the central nervous system (CNS) and peripheral nervous system (PNS) and in large amounts. However, MBP still makes up only 30 per cent of total myelin, so there is good reason for not just looking at MBP but rather at something in the other 70 per cent of myelin that isn’t MBP?

The idea of looking at proteins other than MBP has been adopted by Norwegian bio-pharma Nykode Therapeutics. Its inverse vaccine called TV004 aims to boost immune system tolerance to another protein found in myelin called MOG or myelin oligodendrocyte glycoprotein.

Mog

MOG is abundant in the central nervous system (CNS) but less so in the peripheral nervous system (PNS), and as MS is predominantly a CNS rather than a PNS disease then MOG is a good candidate in the search for developing an inverse vaccine to MS. Better still, early research has shown TV004, through generating tolerance to MOG, was able to prevent the development of MS in a mouse model of the disease. It was found TV004 infusions before ‘mouse MS’ was induced in protected mice from mouse MS, with very mild or no symptoms over 28 days.

Pharmaceutical funding

Another inverse vaccine approach comes from Swiss biopharma Anokion and has the backing of pharmaceutical giant Pfizer who have stumped up $35m. The Anokion researchers point out a basic challenge in inverse vaccines, namely that although several inverse vaccines succeed in animal experiments they often fail in human trials. The reason is that it’s hard to determine exactly what self-antigen the human body is reacting to, and whether it’s reacting to more than one. This is a potential problem in the Nykode research where myelin or MOG (myelin oligodendrocyte glycoprotein) seems to be the obvious auto-antigen but only clinical trials in humans will prove whether this is the reality.

In addition to the question about exactly which myelin protein or proteins cause autoimmunity in MS, there is another question: which body part do you use as a base for targeting these auto-immune causing proteins? Anokion is using a new approach pioneered by Jeffrey Hubbell, the company’s co-founder, and colleagues at the University of Chicago’s Pritzker School of Molecular Engineering.

The liver

The Anokion inverse vaccine ANK-700 directs the self-antigen to the liver — an often-underappreciated immune system player. The liver can signal the immune system to leave certain cells alone and is ideally positioned to detect pathogens entering the body via the gut. The liver is designed to detect, capture and clear bacteria and viruses as it contains the largest collection of phagocytes in the body. Phagocytes are cells that protect the body by ‘hoovering up’ harmful foreign particles, bacteria, and dead cells.

The Anokion vaccines use engineered proteins and a sugar to encourage the liver to label the self-antigen as a friend, not a foe. This can suspend the immune attack, halting and potentially reversing disease progression, a process outlined in a recent study. In terms of the self-antigen that ANK-700 is working on, Anokion says the following – “it encompasses a previously identified myelin antigen that is implicated in driving multiple sclerosis,” so it’s not clear whether it is MOG or something else. The company, however, says the following – “In the past, we showed that we could use our approach to prevent autoimmunity.” It is likely ANK-700 would be given as an introductory dose followed by regular boosters to keep the immune system from ‘veering off track’. In other words, ANK-700 wouldn’t be a one-off treatment.

Human trials in MS are underway, with help of that $35 million from Pfizer. ANK-700 is currently in phase 1 trials at 15 locations in the US. Early results have shown a trend toward immune tolerance and Anokion anticipates having full results very soon.

So, while the idea of a reverse vaccine is very much a wild-card in MS research, early results available next year (2025) may give some indication of whether this new approach could lead to the cure, MS research’s holy grail which, like the crusaders of old, we are all ardently seeking.