Editing Multiple sclerosis (section)

== Research ==
{{Main|Research in multiple sclerosis}}

=== Epstein-Barr virus ===
As of 2022, the pathogenesis of MS, as it relates to [[Epstein–Barr virus|Epstein-Barr virus (EBV)]], is actively investigated, as are disease-modifying therapies; understanding of how risk factors combine with EBV to initiate MS is sought. Whether EBV is the only cause of MS might be better understood if an [[Epstein–Barr virus vaccine|EBV vaccine]] is developed and shown to prevent MS as well.<ref name="Aloisi20222"/>

Even though a variety of studies showed the connection between an EBV infection and a later development of multiple sclerosis, the mechanisms behind this correlation are not completely clear, and several theories have been proposed to explain the relationship between the two diseases. It is thought that the involvement of EBV-infected [[B cell|B-cells]] (B lymphocytes)<ref>{{cite journal | vauthors = Bar-Or A, Pender MP, Khanna R, Steinman L, Hartung HP, Maniar T, Croze E, Aftab BT, Giovannoni G, Joshi MA | title = Epstein-Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies | journal = Trends in Molecular Medicine | volume = 26 | issue = 3 | pages = 296–310 | date = March 2020 | pmid = 31862243 | pmc = 7106557 | doi = 10.1016/j.molmed.2019.11.003 }}</ref> and the involvement of anti-[[EBNA]] antibodies, which appear to be significantly higher in multiple sclerosis patients, play a crucial role in the development of the disease.<ref>{{cite journal | vauthors = DeLorenze GN, Munger KL, Lennette ET, Orentreich N, Vogelman JH, Ascherio A | title = Epstein-Barr virus and multiple sclerosis: evidence of association from a prospective study with long-term follow-up | journal = Archives of Neurology | volume = 63 | issue = 6 | pages = 839–844 | date = June 2006 | pmid = 16606758 | doi = 10.1001/archneur.63.6.noc50328 | doi-access = free }}</ref> This is supported by the fact that treatment against B-cells, e.g. [[ocrelizumab]], reduces the symptoms of multiple sclerosis: annual relapses appear less frequently and the disability progression is slower.<ref>{{cite journal | vauthors = Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L | title = Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis | journal = The New England Journal of Medicine | volume = 376 | issue = 3 | pages = 221–234 | date = January 2017 | pmid = 28002679 | doi = 10.1056/NEJMoa1601277 | s2cid = 205099904 | hdl = 2445/178507 | hdl-access = free }}</ref> A 2022 [[Stanford University]] study has shown that during an EBV infection, molecular mimicry can occur, where the immune system will produce antibodies against the [[EBNA]]1 protein, which at the same time is able to bind to GlialCAM in the myelin. Additionally, they observed a phenomenon which is uncommon in healthy individuals but often detected in multiple sclerosis patients – B-cells are trafficking to the brain and spinal cord, where they are producing oligoclonal antibody bands. A majority of these oligoclonal bands do have an affinity to the viral protein EBNA1, which is cross-reactive to GlialCAM. These antibodies are abundant in approximately 20–25% of multiple sclerosis patients and worsen the autoimmune demyelination which leads consequently to a pathophysiological exacerbation of the disease. Furthermore, the intrathecal oligoclonal expansion with a constant somatic hypermutation is unique in multiple sclerosis when compared to other neuroinflammatory diseases. In the study, there was also the abundance of antibodies with IGHV 3–7 genes measured, which appears to be connected to the disease progress. Antibodies which are IGHV3–7-based are binding with a high affinity to EBNA1 and GlialCAM. This process is actively thriving the demyelination. It is probable that B-cells, expressing IGHV 3–7 genes entered the CSF and underwent affinity maturation after facing GlialCAM, which led consequently to the production of high-affinity anti-GlialCAM antibodies. This was additionally shown in the EAE mouse model where immunization with EBNA1 lead to a strong B-cell response against GlialCAM, which worsened the EAE.<ref>{{cite journal | vauthors = Lanz TV, Brewer RC, Ho PP, Moon JS, Jude KM, Fernandez D, Fernandes RA, Gomez AM, Nadj GS, Bartley CM, Schubert RD, Hawes IA, Vazquez SE, Iyer M, Zuchero JB, Teegen B, Dunn JE, Lock CB, Kipp LB, Cotham VC, Ueberheide BM, Aftab BT, Anderson MS, DeRisi JL, Wilson MR, Bashford-Rogers RJ, Platten M, Garcia KC, Steinman L, Robinson WH | title = Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM | journal = Nature | volume = 603 | issue = 7900 | pages = 321–327 | date = March 2022 | pmid = 35073561 | pmc = 9382663 | doi = 10.1038/s41586-022-04432-7 | bibcode = 2022Natur.603..321L }}</ref>

=== Human endogenous retroviruses ===
Two members of the human endogenous retroviruses-W ([[HERV]]-W) family, namely, ERVWE1 and MS-associated retrovirus (MSRV), may be co-factors in MS immunopathogenesis. HERVs constitute up to 8% of the human genome; most are epigenetically silent, but can be reactivated by exogenous viruses, proinflammatory conditions or oxidative stress.<ref>{{cite journal | vauthors = Morandi E, Tanasescu R, Tarlinton RE, Constantinescu CS, Zhang W, Tench C, Gran B | title = The association between human endogenous retroviruses and multiple sclerosis: A systematic review and meta-analysis | journal = PLOS ONE | volume = 12 | issue = 2 | pages = e0172415 | date = 2017-02-16 | pmid = 28207850 | pmc = 5313176 | doi = 10.1371/journal.pone.0172415 | bibcode = 2017PLoSO..1272415M | veditors = Ruprecht K | doi-access = free }}</ref><ref>{{Cite journal |vauthors=Li Y, Fan T, Cui J |date=March 2022 |title=Human endogenous retroviruses in viral disease and therapy |journal=Clinical and Translational Discovery |language=en |volume=2 |issue=1 |doi=10.1002/ctd2.38 |s2cid=247750447 |doi-access=free }}</ref><ref>{{cite journal | vauthors = Rangel SC, da Silva MD, da Silva AL, Dos Santos JM, Neves LM, Pedrosa A, Rodrigues FM, Trettel CD, Furtado GE, de Barros MP, Bachi AL, Romano CM, Nali LH | title = Human endogenous retroviruses and the inflammatory response: A vicious circle associated with health and illness | journal = Frontiers in Immunology | volume = 13 | pages = 1057791 | date = 2022-11-23 | pmid = 36518758 | pmc = 9744114 | doi = 10.3389/fimmu.2022.1057791 | doi-access = free }}</ref>

=== Medications ===
Medications that influence voltage-gated sodium ion channels are under investigation as a potential neuroprotective strategy because of hypothesized role of sodium in the pathological process leading to axonal injury and accumulating disability. There is insufficient evidence of an effect of sodium channel blockers for people with MS.<ref>{{cite journal | vauthors = Yang C, Hao Z, Zhang L, Zeng L, Wen J | title = Sodium channel blockers for neuroprotection in multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | issue = 10 | pages = CD010422 | date = October 2015 | volume = 2015 | pmid = 26486929 | doi = 10.1002/14651858.CD010422.pub2 | pmc = 9242538 }}</ref>

=== Pathogenesis ===
MS is a clinically defined entity with several atypical presentations. Some auto-antibodies have been found in atypical MS cases, giving birth to separate disease families and restricting the previously wider concept of MS.

[[Aquaporin 4|Anti-AQP4 autoantibodies]] were found in [[neuromyelitis optica]] (NMO), which was previously considered a MS variant. A spectrum of diseases named NMOSD (NMO spectrum diseases) or anti-AQP4 diseases has been accepted.<ref name="Misu">{{cite journal | vauthors = Misu T, Fujihara K | title = Neuromyelitis optica spectrum and myelin oligodendrocyte glycoprotein antibody-related disseminated encephalomyelitis. | journal = Clinical and Experimental Neuroimmunology | date = February 2019 | volume = 10 | issue = 1 | pages= 9–17 | doi = 10.1111/cen3.12491 | doi-access = free }}</ref> Some cases of MS were presenting [[myelin oligodendrocyte glycoprotein|anti-MOG autoantibodies]], mainly overlapping with the Marburg variant. Anti-MOG autoantibodies were found to be also present in ADEM, and a second spectrum of separated diseases is being considered. This spectrum is named inconsistently across different authors, but it is normally something similar to [[Anti-MOG associated encephalomyelitis|anti-MOG demyelinating diseases]].<ref name="Misu" />

A third kind of auto-antibodies is accepted. There are several [[neurofascin|anti-neurofascin]] auto-antibodies that damage the Ranvier nodes of the neurons. These antibodies are more related to the peripheral nervous demyelination, but they were also found in chronic progressive PPMS and [[combined central and peripheral demyelination]] (CCPD, which is considered another atypical MS presentation).<ref name="Kira">{{cite journal | vauthors = Kira JI, Yamasaki R, Ogata H | title = Anti-neurofascin autoantibody and demyelination | journal = Neurochemistry International | volume = 130| pages = 104360| pmid = 30582947 | doi = 10.1016/j.neuint.2018.12.011 | year = 2019 | doi-access = free }}</ref>

In addition to the significance of auto-antibodies in MS, four different patterns of demyelination have been reported, opening the door to consider MS as a [[heterogeneous disease]].<ref name="pmid23917093">{{cite journal | vauthors = Popescu BF, Pirko I, Lucchinetti CF | title = Pathology of multiple sclerosis: where do we stand? | journal = Continuum | volume = 19 | issue = 4 Multiple Sclerosis | pages = 901–21 | date = August 2013 | pmid = 23917093 | pmc = 3915566 | doi = 10.1212/01.CON.0000433291.23091.65 }}</ref>

=== Biomarkers ===
{{Main|Biomarkers of multiple sclerosis}}
[[File:Journal.pone.0057573.g005 cropped.png|thumb|upright|[[Magnetic resonance imaging|MRI]] brain scan produced using a ''Gradient-echo phase sequence'' showing an iron deposit in a white matter lesion (inside green box in the middle of the image; enhanced and marked by red arrow top-left corner)<ref name="pmid23516409">{{cite journal | vauthors = Mehta V, Pei W, Yang G, Li S, Swamy E, Boster A, Schmalbrock P, Pitt D | title = Iron is a sensitive biomarker for inflammation in multiple sclerosis lesions | journal = PLOS ONE | volume = 8 | issue = 3 | pages = e57573 | year = 2013 | pmid = 23516409 | pmc = 3597727 | doi = 10.1371/journal.pone.0057573 | bibcode = 2013PLoSO...857573M | doi-access = free }}</ref>]]

Since disease progression is the result of degeneration of neurons, the roles of proteins showing loss of nerve tissue such as [[neurofilament]]s, [[Tau protein|tau]], and [[N-acetylaspartate]] are under investigation.<ref>{{cite journal | vauthors = Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, Barro C, Kappos L, Comabella M, Fazekas F, Petzold A, Blennow K, Zetterberg H, Kuhle J | title = Neurofilaments as biomarkers in neurological disorders | journal = Nature Reviews. Neurology | volume = 14 | issue = 10 | pages = 577–589 | date = October 2018 | pmid = 30171200 | doi = 10.1038/s41582-018-0058-z | url = https://discovery.ucl.ac.uk/id/eprint/10057189/ }}</ref><ref>{{cite journal | vauthors = Petzold A | title = Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss | journal = Journal of the Neurological Sciences | volume = 233 | issue = 1–2 | pages = 183–98 | date = June 2005 | pmid = 15896809 | doi = 10.1016/j.jns.2005.03.015 | url = https://discovery.ucl.ac.uk/id/eprint/18928/ }}</ref>

Improvement in neuroimaging techniques such as [[positron emission tomography]] (PET) or MRI carry a promise for better diagnosis and prognosis predictions. Regarding MRI, there are several techniques that have already shown some usefulness in research settings and could be introduced into clinical practice, such as double-inversion recovery sequences, [[magnetization transfer]], [[Diffusion MRI#Diffusion tensor imaging|diffusion tensor]], and [[functional magnetic resonance imaging]].<ref name="pmid22159052">{{cite journal | vauthors = Filippi M, Rocca MA, De Stefano N, Enzinger C, Fisher E, Horsfield MA, Inglese M, Pelletier D, Comi G | title = Magnetic resonance techniques in multiple sclerosis: the present and the future | journal = Archives of Neurology | volume = 68 | issue = 12 | pages = 1514–20 | date = December 2011 | pmid = 22159052 | doi = 10.1001/archneurol.2011.914 | doi-access = free }}</ref> These techniques are more specific for the disease than existing ones, but still lack some standardization of acquisition protocols and the creation of normative values.<ref name="pmid22159052" /> This is particularly the case for [[proton magnetic resonance spectroscopy]], for which a number of methodological variations observed in the literature may underlie continued inconsistencies in central nervous system metabolic abnormalities, particularly in [[N-acetyl aspartate]], [[myoinositol]], [[choline]], [[Glutamate (neurotransmitter)|glutamate]], [[GABA]], and [[Glutathione|GSH]], observed for multiple sclerosis and its subtypes.<ref>{{cite journal | vauthors = Swanberg KM, Landheer K, Pitt D, Juchem C | title = Quantifying the Metabolic Signature of Multiple Sclerosis by ''in vivo'' Proton Magnetic Resonance Spectroscopy: Current Challenges and Future Outlook in the Translation From Proton Signal to Diagnostic Biomarker | language = English | journal = Frontiers in Neurology | volume = 10 | pages = 1173 |year = 2019 | pmid = 31803127 | pmc = 6876616 | doi = 10.3389/fneur.2019.01173 | doi-access = free }}</ref> There are other techniques under development that include contrast agents capable of measuring levels of peripheral [[macrophage]]s, inflammation, or neuronal dysfunction,<ref name="pmid22159052" /> and techniques that measure iron deposition that could serve to determine the role of this feature in MS, or that of cerebral perfusion.<ref name="pmid22159052" />

=== COVID-19 ===
The hospitalization rate was found to be higher among individuals with MS and COVID-19 infection, at 10%, while the pooled infection rate is estimated at 4%. The pooled prevalence of death in hospitalized individuals with MS is estimated as 4%.<ref>{{cite journal |vauthors=Moghadasi AN, Mirmosayyeb O, Barzegar M, Sahraian MA, Ghajarzadeh M |title=The prevalence of COVID-19 infection in patients with multiple sclerosis (MS): a systematic review and meta-analysis |journal=Neurol Sci |volume=42 |issue=8 |pages=3093–3099 |date=August 2021 |pmid=34100130 |pmc=8184129 |doi=10.1007/s10072-021-05373-1 }}</ref>

=== Metformin ===
A 2019 study on rats and a 2024 study on mice showed that a first-line medication for the treatment of [[type 2 diabetes]], [[metformin]], could promote [[remyelination]].<ref>{{cite journal | vauthors = Neumann B, Baror R, Zhao C, Segel M, Dietmann S, Rawji KS, Foerster S, McClain CR, Chalut K, van Wijngaarden P, Franklin RJ | title = Metformin Restores CNS Remyelination Capacity by Rejuvenating Aged Stem Cells | journal = Cell Stem Cell | volume = 25 | issue = 4 | pages = 473–485.e8 | date = October 2019 | pmid = 31585093 | pmc = 6863391 | doi = 10.1016/j.stem.2019.08.015 }}</ref><ref>{{cite journal | vauthors = Gilbert EA, Livingston J, Flores EG, Khan M, Kandavel H, Morshead CM | title = Metformin treatment reduces inflammation, dysmyelination and disease severity in a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis | journal = Brain Research | volume = 1822 | pages = 148648 | date = January 2024 | pmid = 37890574 | doi = 10.1016/j.brainres.2023.148648 | doi-access = free }}</ref> The promising drug is currently being researched on humans in the Octopus trials, a multi-arm, multi-stage trial, focussed on testing existing drugs for other conditions on patients with MS.<ref>{{Cite web |date=2023-06-06 |title=New treatment hope as world-first MS mega-trial opens site in Northern Ireland |url=https://www.qub.ac.uk/News/Allnews/featured-research/new-treatment-world-first-ms-mega-trial-opens-site-northern-ireland.html |access-date=2024-07-30 |website=www.qub.ac.uk |language=en |archive-date=30 July 2024 |archive-url=https://web.archive.org/web/20240730074954/https://www.qub.ac.uk/News/Allnews/featured-research/new-treatment-world-first-ms-mega-trial-opens-site-northern-ireland.html |url-status=live }}</ref> Currently, clinical trials on humans are ongoing in [[Belgium]], for patients with non-active progressive MS,<ref>{{cite journal | vauthors = De Keersmaecker AV, Van Doninck E, Popescu V, Willem L, Cambron M, Laureys G, D' Haeseleer M, Bjerke M, Roelant E, Lemmerling M, D'hooghe MB, Derdelinckx J, Reynders T, Willekens B | title = A metformin add-on clinical study in multiple sclerosis to evaluate brain remyelination and neurodegeneration (MACSiMiSE-BRAIN): study protocol for a multi-center randomized placebo controlled clinical trial | language = English | journal = Frontiers in Immunology | volume = 15 | pages = 1362629 | date = 2024-02-21 | pmid = 38680485 | pmc = 11046490 | doi = 10.3389/fimmu.2024.1362629 | doi-access = free }}</ref> in the [[United Kingdom|U.K.]], in combination with [[clemastine]] for the treatment of relapsing-remitting MS,<ref>{{Cite web |title=Can metformin and clemastine repair myelin in people with MS? |url=https://www.mssociety.org.uk/research/explore-our-research/search-our-research-projects/can-metformin-clemastine-repair-myelin-people-MS |access-date=July 30, 2024 |website=MS Society UK |archive-date=30 July 2024 |archive-url=https://web.archive.org/web/20240730074950/https://www.mssociety.org.uk/research/explore-our-research/search-our-research-projects/can-metformin-clemastine-repair-myelin-people-MS |url-status=live }}</ref> and [[Canada]], for MS patients up to 25 years old.<ref>{{Cite web |title=Visual & Neurocognitive Outcomes |url=https://lab.research.sickkids.ca/neuroinflamm/research/visual-neurocognitive-outcomes/ |access-date=2024-07-30 |website=Paediatric Neuroinflammatory Disorders Program |language=en-CA |archive-date=30 July 2024 |archive-url=https://web.archive.org/web/20240730074959/https://lab.research.sickkids.ca/neuroinflamm/research/visual-neurocognitive-outcomes/ |url-status=live }}</ref><ref>{{cite web |title=Metformin |url=https://www.mssociety.org.uk/research/explore-our-research/emerging-research-and-treatments/explore-treatments-in-trials/metformin |website=Multiple Sclerosis Society |access-date=30 July 2024 |archive-date=30 July 2024 |archive-url=https://web.archive.org/web/20240730074951/https://www.mssociety.org.uk/research/explore-our-research/emerging-research-and-treatments/explore-treatments-in-trials/metformin |url-status=live }}</ref>

=== Other emerging theories ===
One emerging hypothesis, referred to as the hygiene hypothesis, suggests that early-life exposure to infectious agents helps to develop the immune system and reduces susceptibility to allergies and autoimmune disorders. The hygiene hypothesis has been linked with MS and [[microbiome]] hypotheses.<ref>{{cite journal | vauthors = Wasko NJ, Nichols F, Clark RB | title = Multiple sclerosis, the microbiome, TLR2, and the hygiene hypothesis | journal = Autoimmunity Reviews | volume = 19 | issue = 1 | pages = 102430 | date = January 2020 | pmid = 31734400 | doi = 10.1016/j.autrev.2019.102430 | doi-access = free }}</ref>

It has also been proposed that certain bacteria found in the gut use molecular mimicry to infiltrate the brain via the [[gut–brain axis]], initiating an inflammatory response and increasing blood-brain barrier permeability. [[Vitamin D]] levels have also been correlated with MS; lower levels of vitamin D correspond to an increased risk of MS, suggesting a reduced prevalence in the tropics – an area with more Vitamin D-rich sunlight – strengthening the impact of geographical location on MS development.<ref>{{cite journal | vauthors = Aranow C | title = Vitamin D and the immune system | journal = Journal of Investigative Medicine | volume = 59 | issue = 6 | pages = 881–886 | date = August 2011 | pmid = 21527855 | pmc = 3166406 | doi = 10.2310/jim.0b013e31821b8755 }}</ref> MS mechanisms begin when peripheral [[Autoreactive lymphocyte|autoreactive]] effector [[CD4+ T cells]] get activated and move into the CNS. [[Antigen-presenting cell]]s localize the reactivation of autoreactive effector CD4-T cells once they have entered the CNS, attracting more T cells and macrophages to form the inflammatory lesion.<ref>{{cite journal | vauthors = Tada T, Takemori T, Okumura K, Nonaka M, Tokuhisa T | title = Two distinct types of helper T cells involved in the secondary antibody response: independent and synergistic effects of Ia- and Ia+ helper T cells | journal = The Journal of Experimental Medicine | volume = 147 | issue = 2 | pages = 446–458 | date = February 1978 | pmid = 415110 | pmc = 2184496 | doi = 10.1084/jem.147.2.446 }}</ref> In MS patients, macrophages and microglia assemble at locations where demyelination and neurodegeneration are actively occurring, and microglial activation is more apparent in the normal-appearing white matter of MS patients.<ref>{{cite journal | vauthors = Lassmann H | title = Multiple Sclerosis Pathology | journal = Cold Spring Harbor Perspectives in Medicine | volume = 8 | issue = 3 | pages = a028936 | date = March 2018 | pmid = 29358320 | pmc = 5830904 | doi = 10.1101/cshperspect.a028936 }}</ref> [[Astrocyte]]s generate neurotoxic chemicals like [[nitric oxide]] and [[TNFα]], attract neurotoxic inflammatory [[monocyte]]s to the CNS, and are responsible for [[astrogliosis]], the scarring that prevents the spread of neuroinflammation and kills neurons inside the scarred area.<ref>{{cite book | vauthors = Minagar A, Shapshak P, Alexander JS | chapter = Pathogenesis of HIV-Associated Dementia and Multiple Sclerosis: Role of Microglia and Astrocytes |date=28 December 2004 | veditors = Aschner M, Costa LG | title = The Role of Glia in Neurotoxicity | edition = 2nd |pages=283–298 |publisher=CRC Press |doi=10.1201/9781420039740-21 |isbn=978-0-429-12860-8 }}</ref>{{Better source needed|reason=Not very recent|date=December 2022}}

In 2024, scientists shared research on their findings of ancient migration to northern Europe from the [[Yamnaya culture|Yamnaya area of culture]],<ref>{{cite journal |vauthors = Allentoft ME, Sikora M, Refoyo-Martínez A, Irving-Pease EK, Fischer A, Barrie W, Ingason A, Stenderup J, Sjögren KG, Pearson A, Sousa da Mota B, Schulz Paulsson B, Halgren A, Macleod R, Jørkov ML, Demeter F, Sørensen L, Nielsen PO, Henriksen RA, Vimala T, McColl H, Margaryan A, Ilardo M, Vaughn A, Fischer Mortensen M, Nielsen AB, Ulfeldt Hede M, Johannsen NN, Rasmussen P, Vinner L, Renaud G, Stern A, Jensen TZ, Scorrano G, Schroeder H, Lysdahl P, Ramsøe AD, Skorobogatov A, Schork AJ, Rosengren A, Ruter A, Outram A, Timoshenko AA, Buzhilova A, Coppa A, Zubova A, Silva AM, Hansen AJ, Gromov A, Logvin A, Gotfredsen AB, Henning Nielsen B, González-Rabanal B, Lalueza-Fox C, McKenzie CJ, Gaunitz C, Blasco C, Liesau C, Martinez-Labarga C, Pozdnyakov DV, Cuenca-Solana D, Lordkipanidze DO, En'shin D, Salazar-García DC, Price TD, Borić D, Kostyleva E, Veselovskaya EV, Usmanova ER, Cappellini E, Brinch Petersen E, Kannegaard E, Radina F, Eylem Yediay F, Duday H, Gutiérrez-Zugasti I, Merts I, Potekhina I, Shevnina I, Altinkaya I, Guilaine J, Hansen J, Aura Tortosa JE, Zilhão J, Vega J, Buck Pedersen K, Tunia K, Zhao L, Mylnikova LN, Larsson L, Metz L, Yepiskoposyan L, Pedersen L, Sarti L, Orlando L, Slimak L, Klassen L, Blank M, González-Morales M, Silvestrini M, Vretemark M, Nesterova MS, Rykun M, Rolfo MF, Szmyt M, Przybyła M, Calattini M, Sablin M, Dobisíková M, Meldgaard M, Johansen M, Berezina N, Card N, Saveliev NA, Poshekhonova O, Rickards O, Lozovskaya OV, Gábor O, Uldum OC, Aurino P, Kosintsev P, Courtaud P, Ríos P, Mortensen P, Lotz P, Persson P, Bangsgaard P, de Barros Damgaard P, Vang Petersen P, Martinez PP, Włodarczak P, Smolyaninov RV, Maring R, Menduiña R, Badalyan R, Iversen R, Turin R, Vasilyev S, Wåhlin S, Borutskaya S, Skochina S, Sørensen SA, Andersen SH, Jørgensen T, Serikov YB, Molodin VI, Smrcka V, Merts V, Appadurai V, Moiseyev V, Magnusson Y, Kjær KH, Lynnerup N, Lawson DJ, Sudmant PH, Rasmussen S, Korneliussen TS, Durbin R, Nielsen R, Delaneau O, Werge T, Racimo F, Kristiansen K, Willerslev E | title=Population genomics of post-glacial western Eurasia |doi-access=free|journal=Nature |date=11 January 2024 |volume=625 |issue=7994 |pages=301–311 |doi=10.1038/s41586-023-06865-0| pmid=38200295 | pmc=10781627 | bibcode=2024Natur.625..301A }}</ref> tracing MS-risk gene variants dating back around 5,000 years.<ref>{{Cite news |vauthors=Johnson CY |date=2024-01-10 |title=Ancient DNA helps trace multiple sclerosis origins in European descendants |url=https://www.washingtonpost.com/science/2024/01/10/ancient-dna-multiple-sclerosis-european-ancestry/ |access-date=2024-01-11 |newspaper=Washington Post |archive-date=17 August 2024 |archive-url=https://web.archive.org/web/20240817130847/https://www.washingtonpost.com/science/2024/01/10/ancient-dna-multiple-sclerosis-european-ancestry/ |url-status=live }}</ref><ref>{{Cite web |vauthors=Roxby P |date=10 January 2024 |title=Scientists crack mystery of how MS gene spread |url=https://www.bbc.com/news/health-67917294 |access-date=2024-01-11 |website=BBC News |language=en-GB |archive-date=11 January 2024 |archive-url=https://web.archive.org/web/20240111083346/https://www.bbc.com/news/health-67917294 |url-status=live }}</ref> The MS-risk gene variants protected ancient cattle herders from animal diseases,<ref>{{cite bioRxiv |vauthors= Barrie W, Yang Y, Irving-Pease E, Attfield KE, Scorrano G, Jensen LT, Armen AP, Dimopoulos EA, Stern A, Refoyo-Martinez A, Pearson A | title =  Elevated genetic risk for multiple sclerosis originated in Steppe Pastoralist populations.  |date=October 6, 2023 |biorxiv=10.1101/2023.10.06.561165|quote=Our findings also support the interpretation of increased pathogen pressure as a driver of positive selection on immunogenetic variants associated with risk of the autoimmune disease multiple sclerosis in Steppe populations around 5,000 years ago[[doi:10.1101/2022.09.23.509097|[59]<nowiki/>]]}}</ref> but modern lifestyles, diets and better hygiene, have allowed the gene to develop, resulting in the higher risk of MS today.<ref>{{Cite web|url=https://www.nationalmssociety.org/About-the-Society/News/Novel-Study-Suggests-that-MS-was-Brought-to-Northe|title=Novel Study Suggests that MS was Brought to Northern Europe 5,000 Years Ago|date=10 January 2024|work=National MS Society|access-date=11 January 2024|archive-date=11 January 2024|archive-url=https://web.archive.org/web/20240111083629/https://www.nationalmssociety.org/About-the-Society/News/Novel-Study-Suggests-that-MS-was-Brought-to-Northe|url-status=live}}</ref>