Thonhoff JR, Simpson EP, Appel SH (2018) Neuroinflammatory mechanisms in amyotrophic lateral sclerosis pathogenesis. Curr Opin Neurol 31(5):635–639

CAS  PubMed  Article  Google Scholar 

Graves MC, Fiala M, Dinglasan LA, Liu NQ, Sayre J, Chiappelli F, van Kooten C, Vinters HV (2004) Inflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells. Amyotroph Lateral Scler Other Motor Neuron Disord 5(4):213–219

CAS  PubMed  Article  Google Scholar 

Kawamata T, Akiyama H, Yamada T, McGeer PL (1992) Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am J Pathol 140(3):691–707

CAS  PubMed  PubMed Central  Google Scholar 

Hall ED, Oostveen JA, Gurney ME (1998) Relationship of microglial and astrocytic activation to disease onset and progression in a transgenic model of familial ALS. Glia 23(3):249–256

CAS  PubMed  Article  Google Scholar 

Hooten KG, Beers DR, Zhao W, Appel SH (2015) Protective and toxic neuroinflammation in amyotrophic lateral sclerosis. Neurotherapeutics 12(2):364–375

CAS  PubMed  PubMed Central  Article  Google Scholar 

Sheean RK, McKay FC, Cretney E, Bye CR, Perera ND, Tomas D, Weston RA, Scheller KJ, Djouma E, Menon P et al (2018) Association of regulatory T-cell expansion with progression of amyotrophic lateral sclerosis: a study of humans and a transgenic mouse model. JAMA Neurol 75(6):681–689

PubMed  PubMed Central  Article  Google Scholar 

Rashid Chehreh Bargh S, Tafakhori A, Masoumi F, Rahmani F, Ahmadi M, Namdar A, Azimi M, Tavasolian P, Habibi S, Zamani B et al (2018) Evaluation of regulatory T lymphocytes and IL2Ra and FOXP3 gene expression in peripheral mononuclear cells from patients with amyotrophic lateral sclerosis. Ir J Med Sci 187(4):1065–1071

CAS  PubMed  Article  Google Scholar 

Zhao W, Beers DR, Liao B, Henkel JS, Appel SH (2012) Regulatory T lymphocytes from ALS mice suppress microglia and effector T lymphocytes through different cytokine-mediated mechanisms. Neurobiol Dis 48(3):418–428

CAS  PubMed  PubMed Central  Article  Google Scholar 

Zhao W, Beers DR, Appel SH (2013) Immune-mediated mechanisms in the pathoprogression of amyotrophic lateral sclerosis. J Neuroimmune Pharmacol 8(4):888–899

PubMed  PubMed Central  Article  Google Scholar 

Wosiski-Kuhn M, Lyon MS, Caress J, Milligan C (2019) Inflammation, immunity, and amyotrophic lateral sclerosis: II. immune-modulating therapies. Muscle Nerve 59(1):23–33

PubMed  Article  Google Scholar 

Gourie-Devi M, Nalini A, Subbakrishna DK (1997) Temporary amelioration of symptoms with intravenous cyclophosphamide in amyotrophic lateral sclerosis. J Neurol Sci 150(2):167–172

CAS  PubMed  Article  Google Scholar 

Smith SA, Miller RG, Murphy JR, Ringel SP (1994) Treatment of ALS with high dose pulse cyclophosphamide. J Neurol Sci 124(Suppl):84–87

PubMed  Article  Google Scholar 

Eglitis MA, Mezey E (1997) Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci USA 94(8):4080–4085

CAS  PubMed  PubMed Central  Article  Google Scholar 

Priller J, Flügel A, Wehner T, Boentert M, Haas CA, Prinz M, Fernández-Klett F, Prass K, Bechmann I, de Boer BA et al (2001) Targeting gene-modified hematopoietic cells to the central nervous system: use of green fluorescent protein uncovers microglial engraftment. Nat Med 7(12):1356–1361

CAS  PubMed  Article  Google Scholar 

Lampron A, Pimentel-Coelho PM, Rivest S (2013) Migration of bone marrow-derived cells into the central nervous system in models of neurodegeneration. J Comp Neurol 521(17):3863–3876

CAS  PubMed  Article  Google Scholar 

Terashima T, Kojima H, Urabe H, Yamakawa I, Ogawa N, Kawai H, Chan L, Maegawa H (2014) Stem cell factor-activated bone marrow ameliorates amyotrophic lateral sclerosis by promoting protective microglial migration. J Neurosci Res 92(7):856–869

CAS  PubMed  PubMed Central  Article  Google Scholar 

Garbuzova-Davis S, Haller E, Navarro S, Besong TE, Boccio KJ, Hailu S, Khatib M, Sanberg PR, Appel SH, Borlongan CV (2018) Transplantation of human bone marrow stem cells into symptomatic ALS mice enhances structural and functional blood-spinal cord barrier repair. Exp Neurol 310:33–47

PubMed  PubMed Central  Article  Google Scholar 

Garbuzova-Davis S, Kurien C, Haller E, Eve DJ, Navarro S, Steiner G, Mahendrasah A, Hailu S, Khatib M, Boccio KJ et al (2015) Human bone marrow endothelial progenitor cell transplantation into symptomatic ALS mice delays disease progression and increases motor neuron survival by repairing blood-spinal cord barrier. Sci Rep 2019 9(1):5280

Google Scholar 

Sharrack B, Saccardi R, Alexander T, Badoglio M, Burman J, Farge D, Greco R, Jessop H, Kazmi M, Kirgizov K et al (2020) Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases: updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE). Bone Marrow Transplant 55(2):283–306

PubMed  Article  Google Scholar 

Muraro PA, Martin R, Mancardi GL, Nicholas R, Sormani MP, Saccardi R (2017) Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis. Nat Rev Neurol 13(7):391–405

CAS  PubMed  Article  Google Scholar 

Muraro PA, Abrahamsson SV (2010) Resetting autoimmunity in the nervous system: the role of hematopoietic stem cell transplantation. Curr Op Investig Drugs 11:1265–1275

CAS  Google Scholar 

Mancardi G, Saccardi R (2008) Autologous haematopoietic stem-cell transplantation in multiple sclerosis. Lancet Neurol 7(7):626–636

PubMed  Article  Google Scholar 

Sormani MP, Muraro PA, Schiavetti I, Signori A, Laroni A, Saccardi R, Mancardi GL (2017) Autologous hematopoietic stem cell transplantation in multiple sclerosis: a meta-analysis [published correction appears in Neurology 2017:11;89(2):215]. Neurology 88(22):2115–2122

PubMed  Article  Google Scholar 

Nash RA, Hutton GJ, Racke MK, Popat U, Devine SM, Steinmiller KC, Griffith LM, Muraro PA, Openshaw H, Sayre PH et al (2017) High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS. Neurology 88(9):842–852

CAS  PubMed  PubMed Central  Article  Google Scholar 

Atkins HL, Bowman M, Allan D, Anstee G, Arnold DL, Bar-Or A, Bence-Bruckler I, Birch P, Bredeson C, Chen J et al (2016) Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial. Lancet 388(10044):576–585

PubMed  Article  Google Scholar 

Curro D, Vuolo L, Gualandi F, Bacigalupo A, Roccatagliata L, Capello E, Uccelli A, Saccardi R, Sormani MP, Mancardi G (2015) Low intensity lympho-ablative regimen followed by autologous hematopoietic stem cell transplantation in severe forms of multiple sclerosis: a MRI-based clinical study. Mult Scler 21(11):1423–1430

CAS  PubMed  Article  Google Scholar 

Leis AA, Ross MA, Verheijde JL, Leis JF (2016) Immunoablation and stem cell transplantation in amyotrophic lateral sclerosis: the ultimate test for the autoimmune pathogenesis hypothesis. Front Neurol 7:12

PubMed  PubMed Central  Google Scholar 

Appel SH, Engelhardt JI, Henkel JS, Siklos L, Beers DR, Yen AA, Simpson EP, Luo Y, Carrum G, Heslop HE et al (2008) Hematopoietic stem cell transplantation in patients with sporadic amyotrophic lateral sclerosis. Neurology 71(17):1326–1334

CAS  PubMed  Article  Google Scholar 

Fournier CN, Schoenfeld D, Berry JD, Cudkowicz ME, Chan J, Quinn C, Brown RH, Salameh JS, Tansey MG, Beers DR et al (2018) An open label study of a novel immunosuppression intervention for the treatment of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 19(3–4):242–249

CAS  PubMed  Article  Google Scholar 

Khalid SI, Ampie L, Kelly R, Ladha SS, Dardis C (2017) Immune modulation in the treatment of amyotrophic lateral sclerosis: a review of clinical trials. Front Neurol 8:486

PubMed  PubMed Central  Article  Google Scholar 

Longinetti E, Fang F (2019) Epidemiology of amyotrophic lateral sclerosis: an update of recent literature. Curr Opin Neurol 32(5):771–776

CAS  PubMed  PubMed Central  Article  Google Scholar 

Lunetta C, Lizio A, Maestri E, Sansone VA, Mora G, Miller RG, Appel SH, Chiò A (2017) Serum C-reactive protein as a prognostic biomarker in amyotrophic lateral sclerosis. JAMA Neurol 74(6):660–667

PubMed  PubMed Central  Article  Google Scholar 

Burt RK, Balabanov R, Burman J, Sharrack B, Snowden JA, Oliveira MC, Fagius J, Rose J, Nelson F, Barreira AA et al (2019) Effect of nonmyeloablative hematopoietic stem cell transplantation vs continued disease-modifying therapy on disease progression in patients with relapsing-remitting multiple sclerosis: a randomized clinical trial. JAMA 321(2):165–174

PubMed  PubMed Central  Article  Google Scholar 

Capotondo A, Milazzo R, Politi LS, Quattrini A, Palini A, Plati T, Merella S, Nonis A, di Serio C, Montini E et al (2012) Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation. Proc Natl Acad Sci USA 109(37):15018–15023

CAS  PubMed  PubMed Central  Article  Google Scholar 

Motataianu A, Barcutean L, Balasa R (2020) Neuroimmunity in amyotrophic lateral sclerosis: focus on microglia. Amyotroph Lateral Scler Frontotemporal Degener 21(3–4):159–166

CAS  PubMed  Article  Google Scholar