Multiple sclerosis is the most common neurological disease in young adults, due to the death of cells called oligodendrocytes. These form the myelin sheaths around the axons of neurons in the central nervous system. Its mission is to ensure the effective and rapid transmission of nerve impulses and, in addition, to provide trophic support (feed) to the long axons that connect the spinal cord, the brain and the rest of the structures of the system.
Multiple sclerosis appears between 20 and 40 years of age and 75% of cases occur in women. Its causes are still unknown, with autoimmune and neurodegenerative components. In addition, it is a chronic, serious and disabling disease (it can cause paraplegia and blindness).
For patients, their families and the health system, multiple sclerosis is a serious clinical and social problem because, apart from the limitations derived from the symptoms themselves, it truncates professional careers and plans of all kinds in the most decisive years of a life.
At the moment it only has immunomodulatory drugs for its treatment. Although they can be of great benefit in slowing down the course of the disease, in most cases they cannot stop it completely, or cure it. In addition, they often have significant side effects and are costly to healthcare systems.
These drugs only address the immunopathological aspects of the disease. The first for which the remyelinating effect (which promotes the replacement of lost myelin) has been shown in a reliable clinical trial is clemastine. The neurorepair effect of this first-generation antihistamine, currently in disuse as such, was published in 2017. However, a final phase III trial remains to be completed to verify its usefulness in treating multiple sclerosis.
Messenger RNA enters the scene
In this scenario, the journal Science published this month a work that has attracted extremely powerful attention. The same group that synthesized the Pfizer / BioNTech vaccine against Covid-19 has successfully tested another messenger RNA (mRNA) vaccine that suppresses symptoms in various animal models of multiple sclerosis.
When studying in detail this article, which is related to a previous study in which they demonstrated immunogenic tolerance in dendritic cells, several points emerge that deserve comment for the general public:
- Treatment with the mRNA “vaccine” (“m1Ψ mRNA” is its exact name) selectively suppresses the immune response of regulatory T lymphocytes against myelin, but not against the rest.
- Treatment with the “vaccine” completely suppresses the development of symptoms in the animal model of multiple sclerosis when applied before symptoms appear (which could be considered as preventive treatment).
- When applied once the animals have symptoms, they revert considerably. The animals recover part or even all of their motility (which the authors themselves attribute to an anti-inflammatory effect, not a repair one).
- The researchers also tested the treatment in mice that develop the pattern of multiple sclerosis on a recurring basis and closer to the most common clinical form seen in patients (relapsing-remitting multiple sclerosis). The symptoms also disappear, not completely but significantly, once they have already started or even during their first peak.
- Treatment suppresses myelin antigen-specific autoreactive T cells (those that attack myelin in disease). In addition, by promoting regulatory T lymphocytes, it makes the immune balance shift towards suppressive forms.
There is a long way to go
With this promising new therapeutic approach, autoimmune diseases such as multiple sclerosis could be treated in a novel way. The production of suitably modified mRNA and its inclusion in liposomal nanoparticles is feasible, fast, relatively inexpensive and, in addition, it would allow tackling the personalized treatment of patients. For example, specifically modified mRNAs could be generated against each identified autoantigen in that patient.
As has been said for the treatment of Covid-19, this type of vaccine represents a revolution in the treatment of many diseases. According to the results in the animal model, also in that plague that is multiple sclerosis.
But we must not forget that it is a preclinical trial and that there is still a long way to go before we can think about seeing this type of treatment in the clinic. Much basic research and sequential clinical trials are needed in patients.
If we were to revolutionize the way of treating the immunopathological aspect of the disease, we would continue in 2021 with several pending challenges:
- Know what causes multiple sclerosis.
- Develop treatments that replace lost oligodendrocytes and myelin.
- To test the effects of different immunomodulatory treatments (including this mRNA vaccine) on the spontaneous remyelinating capacity that the adult brain retains thanks to a fascinating population of cells: oligodendrocyte precursors. These represent between 5 and 8% of the total cells that our brain has, that of healthy adults and, also, that of sick people.
In our laboratory we have obtained very promising results that involve various molecular and cellular mechanisms with which to promote repair (remyelination) and neuroprotection of oligodendrocytes and neurons in animal models of multiple sclerosis. A story that I would like to tell you about soon.
Fernando de Castro Soubriet, Senior Scientist at the CSIC and head of the research group. Neurosciences, Instituto Cajal – CSIC
This article was originally published on The Conversation. Read the original.
