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Acute disseminated encephalomyelitis (ADEM),or acute demyelinating encephalomyelitis,is a rare autoimmune disease marked by a sudden,widespread attack of inflammation in the brain and spinal cord. As well as causing the brain and spinal cord to become inflamed,ADEM also attacks the nerves of the central nervous system and damages their myelin insulation,which,as a result,destroys the white matter. The cause is often a trigger such as from viral infection or vaccinations.
Multiple sclerosis (MS) is an autoimmune disease resulting in damage to the insulating covers of nerve cells in the brain and spinal cord. As a demyelinating disease,MS disrupts the nervous system's ability to transmit signals,resulting in a range of signs and symptoms,including physical,mental,and sometimes psychiatric problems. Symptoms include double vision,vision loss,eye pain,muscle weakness,and loss of sensation or coordination. MS takes several forms,with new symptoms either occurring in isolated attacks or building up over time. In relapsing forms of MS symptoms may disappear completely between attacks,although some permanent neurological problems often remain,especially as the disease advances. In progressive forms of MS,bodily function slowly deteriorates once symptoms manifest and will steadily worsen if left untreated.
Neuromyelitis optica spectrum disorders (NMOSD) are a spectrum of autoimmune diseases characterized by acute inflammation of the optic nerve and the spinal cord (myelitis). Episodes of ON and myelitis can be simultaneous or successive. A relapsing disease course is common,especially in untreated patients.
Myelin oligodendrocyte glycoprotein (MOG) is a glycoprotein believed to be important in the myelination of nerves in the central nervous system (CNS). In humans this protein is encoded by the MOG gene. It is speculated to serve as a necessary "adhesion molecule" to provide structural integrity to the myelin sheath and is known to develop late on the oligodendrocyte.
Experimental autoimmune encephalomyelitis,sometimes experimental allergic encephalomyelitis (EAE),is an animal model of brain inflammation. It is an inflammatory demyelinating disease of the central nervous system (CNS). It is mostly used with rodents and is widely studied as an animal model of the human CNS demyelinating diseases,including multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). EAE is also the prototype for T-cell-mediated autoimmune disease in general.
A neurodegenerative disease is caused by the progressive loss of neurons,in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis,multiple sclerosis,Parkinson's disease,Alzheimer's disease,Huntington's disease,multiple system atrophy,tauopathies,and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry,ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons,these diseases are considered to be incurable;however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level,including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.
Multiple sclerosis is an inflammatory demyelinating disease of the CNS in which activated immune cells invade the central nervous system and cause inflammation,neurodegeneration,and tissue damage. The underlying cause is currently unknown. Current research in neuropathology,neuroimmunology,neurobiology,and neuroimaging,together with clinical neurology,provide support for the notion that MS is not a single disease but rather a spectrum.
Multiple sclerosis and other demyelinating diseases of the central nervous system (CNS) produce lesions and glial scars or scleroses. They present different shapes and histological findings according to the underlying condition that produces them.
Remyelination is the process of propagating oligodendrocyte precursor cells to form oligodendrocytes to create new myelin sheaths on demyelinated axons in the Central nervous system (CNS). This is a process naturally regulated in the body and tends to be very efficient in a healthy CNS. The process creates a thinner myelin sheath than normal,but it helps to protect the axon from further damage,from overall degeneration,and proves to increase conductance once again. The processes underlying remyelination are under investigation in the hope of finding treatments for demyelinating diseases,such as multiple sclerosis.
Inflammatory demyelinating diseases (IDDs),sometimes called Idiopathic (IIDDs) due to the unknown etiology of some of them,are a heterogenous group of demyelinating diseases - conditions that cause damage to myelin,the protective sheath of nerve fibers - that occur against the background of an acute or chronic inflammatory process. IDDs share characteristics with and are often grouped together under Multiple Sclerosis. They are sometimes considered different diseases from Multiple Sclerosis,but considered by others to form a spectrum differing only in terms of chronicity,severity,and clinical course.
Research in multiple sclerosis may find new pathways to interact with the disease,improve function,curtail attacks,or limit the progression of the underlying disease. Many treatments already in clinical trials involve drugs that are used in other diseases or medications that have not been designed specifically for multiple sclerosis. There are also trials involving the combination of drugs that are already in use for multiple sclerosis. Finally,there are also many basic investigations that try to understand the disease better and in the future may help to find new treatments.
Michael Sela was an Israeli immunologist of Polish Jewish origin. He was the W. Garfield Weston Professor of Immunology at the Weizmann Institute of Science in Rehovot. He was a president of the Weizmann Institute of Science.
Programmed cell death protein 1(PD-1),. PD-1 is a protein encoded in humans by the PDCD1 gene. PD-1 is a cell surface receptor on T cells and B cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. This prevents autoimmune diseases,but it can also prevent the immune system from killing cancer cells.
Hartmut Wekerle is a German medical scientist and neurobiologist. He is an emeritus director at the Max Planck Institute of Neurobiology and was the head of the department of Neuroimmunology until 2012.
Protective autoimmunity is a condition in which cells of the adaptive immune system contribute to maintenance of the functional integrity of a tissue,or facilitate its repair following an insult. The term ‘protective autoimmunity’was coined by Prof. Michal Schwartz of the Weizmann Institute of Science (Israel),whose pioneering studies were the first to demonstrate that autoimmune T lymphocytes can have a beneficial role in repair,following an injury to the central nervous system (CNS). Most of the studies on the phenomenon of protective autoimmunity were conducted in experimental settings of various CNS pathologies and thus reside within the scientific discipline of neuroimmunology.
Tumefactive multiple sclerosis is a condition in which the central nervous system of a person has multiple demyelinating lesions with atypical characteristics for those of standard multiple sclerosis (MS). It is called tumefactive as the lesions are "tumor-like" and they mimic tumors clinically,radiologically and sometimes pathologically.
Multiple sclerosis (MS) can be pathologically defined as the presence of distributed glial scars (scleroses) in the central nervous system that must show dissemination in time (DIT) and in space (DIS) to be considered MS lesions.
MOG antibody disease (MOGAD) or MOG antibody-associated encephalomyelitis (MOG-EM) is an inflammatory demyelinating disease of the central nervous system. Serum anti-myelin oligodendrocyte glycoprotein antibodies are present in up to half of patients with an acquired demyelinating syndrome and have been described in association with a range of phenotypic presentations,including acute disseminated encephalomyelitis,optic neuritis,transverse myelitis,and neuromyelitis optica.
Several biomarkers for diagnosis of multiple sclerosis,disease evolution and response to medication are under research. While most of them are still under research,there are some of them already well stablished:
Robyn S. Klein is an American neuroimmunologist as well as the Vice Provost and Associate Dean for Graduate Education at Washington University in St. Louis. Klein is also a professor in the Departments of Medicine,Anatomy &Neurobiology,and Pathology &Immunology. Her research explores the pathogenesis of neuroinflammation in the central nervous system by probing how immune signalling molecules regulate blood brain barrier permeability. Klein is also a fervent advocate for gender equity in STEM,publishing mechanisms to improve gender equity in speakers at conferences,participating nationally on gender equity discussion panels,and through service as the president of the Academic Women’s Network at the Washington University School of Medicine.
References
- ↑ "Lawrence Steinman, MD".
- 1 2 3 "DIRECTOR - Himalaya Therapeutics".
- ↑ "Current Steinman Lab Members".
- 1 2 "John Dystel Prize".
- 1 2 "Prize for research on multiple sclerosis goes to Lawrence Steinman".
- 1 2 "The Anthony Cerami Award in Translational Medicine".
- ↑ "Scientific Advisory Board - Arete Discoveries".
- ↑ "Lawrence Steinman Stanford University School of Medicine".
- ↑ "Scientific Advisory Board - Applied Therapeutics".
- ↑ Davis, T. (2016). "Profile of Lawrence Steinman". Proceedings of the National Academy of Sciences of the United States of America. 113 (6): 1468–1470. doi: 10.1073/pnas.1600083113 . PMC 4760808 . PMID 26811468.
- ↑ "Larry Steinman". Neuron. 110 (21): 3412–3414. 2 November 2022. doi:10.1016/j.neuron.2022.10.012.
- ↑ "Brief Bio".
- ↑ "Dr. Lawrence Steinman MD".
- ↑ "Lawrence Steinman, MD — Co-Chair".
- ↑ "About Tolerion".
- ↑ "Transparency Life Sciences Awarded $1.4 Million NCATS SBIR Grant To Conduct Innovative Trial Of Lisinopril In Multiple Sclerosis". 8 September 2014.
- ↑ "Startups on the menu: Atreca". Nature Biotechnology. 33 (5): 444. 2015. doi:10.1038/nbt.3226.
- ↑ "Lawrence Steinman, MD".
- ↑ "About the PNAS Member Editor".
- ↑ Yednock, Ted A.; Cannon, Catherine; Fritz, Lawrence C.; Sanchez-Madrid, Francisco; Steinman, Lawrence; Karin, Nathan (1992). "Prevention of experimental autoimmune encephalomyelitis by antibodies against α4βl integrin". Nature. 356 (6364): 63–66. doi:10.1038/356063a0. PMID 1538783.
- ↑ Lock, Christopher; Hermans, Guy; Pedotti, Rosetta; Brendolan, Andrea; Schadt, Eric; Garren, Hideki; Langer-Gould, Annette; Strober, Samuel; Cannella, Barbara; Allard, John; Klonowski, Paul; Austin, Angela; Lad, Nagin; Kaminski, Naftali; Galli, Stephen J.; Oksenberg, Jorge R.; Raine, Cedric S.; Heller, Renu; Steinman, Lawrence (2002). "Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis". Nature Medicine. 8 (5): 500–508. doi:10.1038/nm0502-500.
- ↑ Steinman, Lawrence (2014). "Immunology of Relapse and Remission in Multiple Sclerosis". Annual Review of Immunology. 32: 257–281. doi:10.1146/annurev-immunol-032713-120227. PMID 24438352.
- ↑ "Design of effective immunotherapy for human autoimmunity".
- 1 2 Ho, Peggy P.; Kanter, Jennifer L.; Johnson, Amanda M.; Srinagesh, Hrishikesh K.; Chang, Eun-Ju; Purdy, Timothy M.; Van Haren, Keith; Wikoff, William R.; Kind, Tobias; Khademi, Mohsen; Matloff, Laura Y.; Narayana, Sirisha; Hur, Eun Mi; Lindstrom, Tamsin M.; He, Zhigang; Fiehn, Oliver; Olsson, Tomas; Han, Xianlin; Han, May H.; Steinman, Lawrence; Robinson, William H. (2012). "Identification of Naturally Occurring Fatty Acids of the Myelin Sheath That Resolve Neuroinflammation". Science Translational Medicine. 4 (137): 137ra73. doi:10.1126/scitranslmed.3003831. PMC 3953135 . PMID 22674551.
- 1 2 Steinman, Lawrence (2015). "No quiet surrender: molecular guardians in multiple sclerosis brain". Journal of Clinical Investigation. 125 (4): 1371–1378. doi:10.1172/JCI74255. PMC 4396493 . PMID 25831441.
- ↑ Steinman, Lawrence (2009). "A molecular trio in relapse and remission in multiple sclerosis". Nature Reviews Immunology. 9 (6): 440–447. doi:10.1038/nri2548. PMID 19444308.
- ↑ Steinman, Lawrence; Fox, Edward; Hartung, Hans-Peter; Alvarez, Enrique; Qian, Peiqing; Wray, Sibyl; Robertson, Derrick; Huang, Deren; Selmaj, Krzysztof; Wynn, Daniel; Cutter, Gary; Mok, Koby; Hsu, Yanzhi; Xu, Yihuan; Weiss, Michael S.; Bosco, Jenna A.; Power, Sean A.; Lee, Lily; Miskin, Hari P.; Cree, Bruce A.C. (2022). "Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis". New England Journal of Medicine. 387 (8): 704–714. doi:10.1056/NEJMoa2201904. PMID 36001711.
- ↑ Garren, Hideki; Robinson, William H.; Krasulová, Eva; Havrdová, Eva; Nadj, Congor; Selmaj, Krzysztof; Losy, Jacek; Nadj, Ilinka; Radue, Ernst-Wilhelm; Kidd, Brian A.; Gianettoni, Jill; Tersini, Karen; Utz, Paul J.; Valone, Frank; Steinman, Lawrence; BHT-3009 Study Group (2008). "Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis". Annals of Neurology. 63 (5): 611–620. doi:10.1002/ana.21370. PMID 18481290.
{{cite journal}}: CS1 maint: numeric names: authors list (link) - ↑ Oksenberg, Jorge R.; Stuart, Simon; Begovich, Ann B.; Bell, Robert B.; Erlich, Henry A.; Steinman, Lawrence; Bernard, Claude C. A. (1990). "Limited heterogeneity of rearranged T-cell receptor Vα transcripts in brains of multiple sclerosis patients". Nature. 345 (6273): 344–346. doi:10.1038/345344a0. PMID 1971424.
- ↑ Oksenberg, Jorge R.; Panzara, Michael A.; Begovich, Ann B.; Mitchell, Dennis; Erlich, Henry A.; Murray, Ronald S.; Shimonkevitz, Richard; Sherritt, Martina; Rothbard, Jonathan; Bernard, Claude C. A.; Steinman, Lawrence (1993). "Selection for T-cell receptor Vβ–Dβ–Jβ gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis". Nature. 362 (6415): 68–70. doi:10.1038/362068a0.
- ↑ Zhang, Monan Angela; Rego, Dorothy; Moshkova, Marina; Kebir, Hania; Chruscinski, Andrzej; Nguyen, Hoangkim; Akkermann, Rainer; Stanczyk, Frank Z.; Prat, Alexandre; Steinman, Lawrence; Dunn, Shannon E. (2012). "Peroxisome proliferator-activated receptor (PPAR)α and -γ regulate IFNγ and IL-17A production by human T cells in a sex-specific way". Proceedings of the National Academy of Sciences. 109 (24): 9505–9510. doi: 10.1073/pnas.1118458109 . PMC 3386070 . PMID 22647601.
- ↑ Rothbard, J. B.; Kurnellas, M. P.; Ousman, S. S.; Brownell, S.; Rothbard, J. J.; Steinman, L. (2019). "Small Heat Shock Proteins, Amyloid Fibrils, and Nicotine Stimulate a Common Immune Suppressive Pathway with Implications for Future Therapies". Cold Spring Harbor Perspectives in Medicine. 9 (7): a034223. doi:10.1101/cshperspect.a034223. PMC 6601455 . PMID 30249602.
- ↑ "Lawrence Steinman honored for research on ties between EBV, MS". 20 February 2023.
- ↑ "Lawrence Steinman". 6 April 2023.