Feldman EL, Goutman SA, Petri S, Mazzini L, Savelieff MG, Shaw PJ, et al. Amyotrophic lateral sclerosis. Lancet. 2022;400(10360):1363–80.
Masrori P, Van Damme P. Amyotrophic lateral sclerosis: a clinical review. Eur J Neurol. 2020;27(10):1918–29.
Petrucelli L, Gitler AD. Unlocking the mystery of ALS. Sci Am. 2017;316(6):46–51.
Mehta P, Raymond J, Nair T, Han M, Berry J, Punjani R et al. Amyotrophic lateral sclerosis estimated prevalence cases from 2022 to 2030, data from the National ALS registry. Amyotroph Lateral Scler Frontotemporal Degeneration. 2025:1–6.
Seals RM, Hansen J, Gredal O, Weisskopf MG. Age-period-cohort analysis of trends in amyotrophic lateral sclerosis in Denmark, 1970–2009. Am J Epidemiol. 2013;178(8):1265–71.
Chio A. Risk factors in the early diagnosis of ALS: European epidemiological studies. Amyotroph Lateral Scler Other Motor Neuron Disorders. 2000;1(sup1):S13–8.
French PW, Ludowyke RI, Guillemin GJ. Fungal-contaminated grass and well water and sporadic amyotrophic lateral sclerosis. Neural Regeneration Res. 2019;14(9):1490–3.
Vinceti M, Bottecchi I, Fan A, Finkelstein Y, Mandrioli J. Are environmental exposures to selenium, heavy metals, and pesticides risk factors for amyotrophic lateral sclerosis? 2012.
Banack SA, Caller TA, Stommel EW. The cyanobacteria derived toxin beta-N-methylamino-L-alanine and amyotrophic lateral sclerosis. Toxins. 2010;2(12):2837–50.
Wang H, O’Reilly ÉJ, Weisskopf MG, Logroscino G, McCullough ML, Thun MJ, et al. Smoking and risk of amyotrophic lateral sclerosis: a pooled analysis of 5 prospective cohorts. Arch Neurol. 2011;68(2):207–13.
Chapman L, Cooper-Knock J, Shaw PJ. Physical activity as an exogenous risk factor for amyotrophic lateral sclerosis: a review of the evidence. Brain. 2023;146(5):1745–57.
Gu A, Zhang Y, He J, Zhao M, Ding L, Liu W, et al. Chronic oxidative stress and stress granule formation in UBQLN2 ALS neurons: insights into neuronal degeneration and potential therapeutic targets. Int J Mol Sci. 2024;25(24):13448.
Oda M, Izumi Y, Kaji R. Gene mutations in Familial amyotrophic lateral sclerosis. Brain Nerve = Shinkei Kenkyu No Shinpo. 2011;63(2):165–70.
Millecamps S, Boillée S, Le Ber I, Seilhean D, Teyssou E, Giraudeau M, et al. Phenotype difference between ALS patients with expanded repeats in C9ORF72 and patients with mutations in other ALS-related genes. J Med Genet. 2012;49(4):258–63.
Abramzon YA, Fratta P, Traynor BJ, Chia R. The overlapping genetics of amyotrophic lateral sclerosis and frontotemporal dementia. Front NeuroSci. 2020;14:42.
Fang T, Je G, Pacut P, Keyhanian K, Gao J, Ghasemi M. Gene therapy in amyotrophic lateral sclerosis. Cells. 2022;11(13):2066.
Benson BC, Shaw PJ, Azzouz M, Highley JR, Hautbergue GM. Proteinopathies as hallmarks of impaired gene expression, proteostasis and mitochondrial function in amyotrophic lateral sclerosis. Front NeuroSci. 2021;15:783624.
Lattante S, Rouleau GA, Kabashi E. TARDBP and FUS mutations associated with amyotrophic lateral sclerosis: summary and update. Hum Mutat. 2013;34(6):812–26.
Scarian E, Fiamingo G, Diamanti L, Palmieri I, Gagliardi S, Pansarasa O. The role of VCP mutations in the spectrum of amyotrophic lateral sclerosis—frontotemporal dementia. Front Neurol. 2022;13:841394.
Trojsi F, Monsurrò MR, Tedeschi G. Exposure to environmental toxicants and pathogenesis of amyotrophic lateral sclerosis: state of the Art and research perspectives. Int J Mol Sci. 2013;14(8):15286–311.
Hernan-Godoy M, Rouaux C. From environment to gene expression: epigenetic methylations and one-carbon metabolism in amyotrophic lateral sclerosis. Cells. 2024;13(11):967.
Kadena K, Vlamos P. Elucidating the epigenetic and protein interaction landscapes in amyotrophic lateral sclerosis: an integrated bioinformatics analysis. Sclerosis. 2024;2(3):140–55.
Dey B, Kumar A, Patel AB. Pathomechanistic networks of motor system injury in amyotrophic lateral sclerosis. Curr Neuropharmacol. 2024;22(11):1778–806.
Matamala JM, Moreno-Roco J, Acosta I, Hughes R, Lillo P, Casar JC, et al. Multidisciplinary care and therapeutic advances in amyotrophic lateral sclerosis. Rev Med Chil. 2022;150(12):1633–46.
Schultz J. Disease-modifying treatment of amyotrophic lateral sclerosis. Am J Manag Care. 2018;24(15 Suppl):S327–35.
Raymond J, Oskarsson B, Mehta P, Horton K. Clinical characteristics of a large cohort of US participants enrolled in the National amyotrophic lateral sclerosis (ALS) Registry, 2010–2015. Amyotroph Lateral Scler Frontotemporal Degeneration. 2019;20(5–6):413–20.
Walhout R, Verstraete E, Van Den Heuvel MP, Veldink JH, Van Den Berg LH. Patterns of symptom development in patients with motor neuron disease. Amyotroph Lateral Scler Frontotemporal Degeneration. 2018;19(1–2):21–8.
Kim H-J, de Leon M, Wang X, Kim HY, Lee Y-J, Kim Y-H, et al. Relationship between clinical parameters and brain structure in sporadic amyotrophic lateral sclerosis patients according to onset type: a voxel-based morphometric study. PLoS ONE. 2017;12(1):e0168424.
Shoesmith CL, Findlater K, Rowe A, Strong MJ. Prognosis of amyotrophic lateral sclerosis with respiratory onset. J Neurol Neurosurg Psychiatry. 2007;78(6):629–31.
Gautier G, Verschueren A, Monnier A, Attarian S, Salort-Campana E, Pouget J. ALS with respiratory onset: clinical features and effects of non-invasive ventilation on the prognosis. Amyotroph Lateral Scler. 2010;11(4):379–82.
Lee JW, Kang S-W, Choi WA. Clinical course of amyotrophic lateral sclerosis according to initial symptoms: an analysis of 500 cases. Yonsei Med J. 2021;62(4):338.
Statland JM, Barohn RJ, Dimachkie MM, Floeter MK, Mitsumoto H. Primary lateral sclerosis. Neurol Clin. 2015;33(4):749.
Gordon P, Cheng B, Katz I, Pinto M, Hays A, Mitsumoto H, et al. The natural history of primary lateral sclerosis. Neurology. 2006;66(5):647–53.
Vacchiano V, Bonan L, Liguori R, Rizzo G. Primary lateral sclerosis: an overview. J Clin Med. 2024;13(2):578.
Liewluck T, Saperstein DS. Progressive muscular atrophy. Neurol Clin. 2015;33(4):761–73.
Kim W-K, Liu X, Sandner J, Pasmantier M, Andrews J, Rowland L, et al. Study of 962 patients indicates progressive muscular atrophy is a form of ALS. Neurology. 2009;73(20):1686–92.
Wijesekera L, Mathers S, Talman P, Galtrey C, Parkinson M, Ganesalingam J, et al. Natural history and clinical features of the flail arm and flail leg ALS variants. Neurology. 2009;72(12):1087–94.
Zhang H, Chen L, Tian J, Fan D. Differentiating slowly progressive subtype of lower limb onset ALS from typical ALS depends on the time of disease progression and phenotype. Front Neurol. 2022;13:872500.
Corcia P, Bede P, Pradat P-F, Couratier P, Vucic S, de Carvalho M. Split-hand and split-limb phenomena in amyotrophic lateral sclerosis: pathophysiology, electrophysiology and clinical manifestations. J Neurol Neurosurg Psychiatry. 2021;92(10):1126–30.
Sonoo M, Takahashi K, Hamada Y, Hokkoku K, Kobayashi S. Split-finger syndrome in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2020;91(11):1235–6.
Jiang Q, Lin J, Wei Q, Yang T, Hou Y, Zhang L, et al. Amyotrophic lateral sclerosis patients with various gene mutations show diverse motor phenotypes and survival in China. J Med Genet. 2024;61(9):839–46.
Millecamps S, Salachas F, Cazeneuve C, Gordon P, Bricka B, Camuzat A, et al. SOD1, ANG, VAPB, TARDBP, and FUS mutations in Familial amyotrophic lateral sclerosis: genotype–phenotype correlations. J Med Genet. 2010;47(8):554–60.
Manohar V, Crowley L, Sreedharan J. TARDBP-related amyotrophic lateral sclerosis-frontotemporal dementia. 2015.
Orban P, Devon RS, Hayden MR, Leavitt BR. Chapter 15 juvenile amyotrophic lateral sclerosis. Handb Clin Neurol. 2007;82:301–12.
Grad LI, Yerbury JJ, Turner BJ, Guest WC, Pokrishevsky E, O’Neill MA et al. Intercellular propagated misfolding of wild-type Cu/Zn superoxide dismutase occurs via exosome-dependent and-independent mechanisms. Proceedings of the National Academy of Sciences. 2014;111(9):3620-5.
Provenzano F, Torazza C, Bonifacino T, Bonanno G, Milanese M. The key role of astrocytes in amyotrophic lateral sclerosis and their commitment to glutamate excitotoxicity. Int J Mol Sci. 2023;24(20):15430.
do Rêgo ACM, Araújo-Filho I. Cellular and molecular mechanisms in neurodegenerative disorders: A comprehensive scoping review. Int J Innovative Res Med Sci (IJIRMS). 2024;9(10).
Todd TW, Petrucelli L. Insights into the pathogenic mechanisms of chromosome 9 open reading frame 72 (C9orf72) repeat expansions. J Neurochem. 2016;138:145–62.
Babić Leko M, Župunski V, Kirincich J, Smilović D, Hortobágyi T, Hof PR, et al. Molecular mechanisms of neurodegeneration related to C9orf72 hexanucleotide repeat expansion. Behav Neurol. 2019;2019(1):2909168.
Kabashi E, Valdmanis PN, Dion P, Rouleau GA. Oxidized/misfolded superoxide dismutase-1: the cause of all amyotrophic lateral sclerosis? Annals of neurology. Official J Am Neurol Association Child Neurol Soc. 2007;62(6):553–9.
Takeuchi H, Kobayashi Y, Ishigaki S, Doyu M, Sobue G. Mitochondrial localization of mutant superoxide dismutase 1 triggers caspase-dependent cell death in a cellular model of Familial amyotrophic lateral sclerosis. J Biol Chem. 2002;277(52):50966–72.
Kabashi E, Lin L, Tradewell ML, Dion PA, Bercier V, Bourgouin P, et al. Gain and loss of function of ALS-related mutations of TARDBP (TDP-43) cause motor deficits in vivo. Hum Mol Genet. 2010;19(4):671–83.
Kon T, Mori F, Tanji K, Miki Y, Toyoshima Y, Yoshida M, et al. ALS-associated protein FIG4 is localized in P Ick and L Ewy bodies, and also neuronal nuclear inclusions, in polyglutamine and intranuclear inclusion body diseases. Neuropathology. 2014;34(1):19–26.
Zhao S, Chen R, Gao Y, Lu Y, Bai X, Zhang J. Fundamental roles of the optineurin gene in the molecular pathology of amyotrophic lateral sclerosis. Front NeuroSci. 2023;17:1319706.
Bagyinszky E, Hulme J, An SSA. Studies of genetic and proteomic risk factors of amyotrophic lateral sclerosis inspire biomarker development and gene therapy. Cells. 2023;12(15):1948.
Deneubourg C, Ramm M, Smith LJ, Baron O, Singh K, Byrne SC, et al. The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy. Autophagy. 2022;18(3):496–517.
Atkin JD, Farg MA, Turner BJ, Tomas D, Lysaght JA, Nunan J, et al. Induction of the unfolded protein response in Familial amyotrophic lateral sclerosis and association of protein-disulfide isomerase with superoxide dismutase 1. J Biol Chem. 2006;281(40):30152–65.
Sasaki S. Endoplasmic reticulum stress in motor neurons of the spinal cord in sporadic amyotrophic lateral sclerosis. J Neuropathology Experimental Neurol. 2010;69(4):346–55.
Santos LS, Moreira-de-Carvalho GOA, Fortes FSA, de Souza ALF. Autophagy Pathways, Ubiquitin-Proteasome system and neurodegenerative diseases: a scopus review. Brazilian J Biol Sci. 2025;12(26):e149–e.
Zheng Q, Huang T, Zhang L, Zhou Y, Luo H, Xu H, et al. Dysregulation of ubiquitin-proteasome system in neurodegenerative diseases. Front Aging Neurosci. 2016;8:303.
Almikhlafi MA, Karami MM, Jana A, Alqurashi TM, Majrashi M, Alghamdi BS, et al. Mitochondrial medicine: A promising therapeutic option against various neurodegenerative disorders. Curr Neuropharmacol. 2023;21(5):1165–83.
Magrané J, Sahawneh MA, Przedborski S, Estévez ÁG, Manfredi G. Mitochondrial dynamics and bioenergetic dysfunction is associated with synaptic alterations in mutant SOD1 motor neurons. J Neurosci. 2012;32(1):229–42.
Burstein S, Valsecchi F, Kawamata H, Bourens M, Zeng R, Zuberi A, et al. In vitro and in vivo studies of the ALS-FTLD protein CHCHD10 reveal novel mitochondrial topology and protein interactions. Hum Mol Genet. 2018;27(1):160–77.
Edens BM, Miller N, Ma Y-C. Impaired autophagy and defective mitochondrial function: converging paths on the road to motor neuron degeneration. Front Cell Neurosci. 2016;10:44.
Kim K, Lee SG, Kegelman TP, Su ZZ, Das SK, Dash R, et al. Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics. J Cell Physiol. 2011;226(10):2484–93.
Heath PR, Shaw PJ. Update on the glutamatergic neurotransmitter system and the role of excitotoxicity in amyotrophic lateral sclerosis. Muscle Nerve: Official J Am Association Electrodiagn Med. 2002;26(4):438–58.
Fontana IC, Souza DG, Souza DO, Gee A, Zimmer ER, Bongarzone S. A medicinal chemistry perspective on excitatory amino acid transporter 2 dysfunction in neurodegenerative diseases. J Med Chem. 2023;66(4):2330–46.
Kawahara Y, Kwak S. Excitotoxicity and ALS: what is unique about the AMPA receptors expressed on spinal motor neurons? Amyotroph Lateral Scler. 2005;6(3):131–44.
Bogaert E, d’Ydewalle C, Van Den Bosch L. Amyotrophic lateral sclerosis and excitotoxicity: from pathological mechanism to therapeutic target. CNS Neurol Disorders-Drug Targets-CNS Neurol Disorders. 2010;9(3):297–304.
Kaus A, Sareen D. ALS patient stem cells for unveiling disease signatures of motoneuron susceptibility: perspectives on the deadly mitochondria, ER stress and calcium triad. Front Cell Neurosci. 2015;9:448.
You J, Youssef MM, Santos JR, Lee J, Park J. Microglia and astrocytes in amyotrophic lateral sclerosis: disease-associated states, pathological roles, and therapeutic potential. Biology. 2023;12(10):1307.
Ziff OJ, Clarke BE, Taha DM, Crerar H, Luscombe NM, Patani R. Meta-analysis of human and mouse ALS astrocytes reveals multi-omic signatures of inflammatory reactive States. Genome Res. 2022;32(1):71–84.
Shin JH, Cho SI, Lim HR, Lee JK, Lee YA, Noh JS, et al. Concurrent administration of Neu2000 and lithium produces marked improvement of motor neuron survival, motor function, and mortality in a mouse model of amyotrophic lateral sclerosis. Mol Pharmacol. 2007;71(4):965–75.
Bilsland LG, Sahai E, Kelly G, Golding M, Greensmith L, Schiavo G. Deficits in axonal transport precede ALS symptoms in vivo. Proceedings of the National Academy of Sciences. 2010;107(47):20523-8.
Ikenaka K, Katsuno M, Kawai K, Ishigaki S, Tanaka F, Sobue G. Disruption of axonal transport in motor neuron diseases. Int J Mol Sci. 2012;13(1):1225–38.
Su XW, Broach JR, Connor JR, Gerhard GS, Simmons Z. Genetic heterogeneity of amyotrophic lateral sclerosis: implications for clinical practice and research. Muscle Nerve. 2014;49(6):786–803.
Pérez-Brangulí F, Mishra HK, Prots I, Havlicek S, Kohl Z, Saul D, et al. Dysfunction of Spatacsin leads to axonal pathology in SPG11-linked hereditary spastic paraplegia. Hum Mol Genet. 2014;23(18):4859–74.
Parveen S, Showkat F, Badesra N, Dar MS, Maqbool T, Dar MJ. Axonal Degeneration, impaired axonal Transport, and synaptic dysfunction in motor neuron Disorder. Mechanism and genetic susceptibility of neurological disorders. Springer; 2024. pp. 199–229.
Sako W, Ito H, Yoshida M, Koizumi H, Kamada M, Fujita K, et al. Nuclear factor κ B expression in patients with sporadic amyotrophic lateral sclerosis and hereditary amyotrophic lateral sclerosis with optineurin mutations. Clin Neuropathol. 2012;31(6):418–23.
Källstig EC. The role of the NF-kappaB pathway in amyotrophic lateral sclerosis pathogenesis. EPFL; 2023.
Fadaka AO, Ojo OA, Osukoya OA, Akuboh O, Ajiboye BO. Role of p38 MAPK signaling in neurodegenerative diseases: a mechanistic perspective. Ann Neurodegener Dis. 2017;2:1026.
Sahana T, Zhang K. Mitogen-activated protein kinase pathway in amyotrophic lateral sclerosis. Biomedicines. 2021;9(8):969.
N-M JA, LeS FdC, R-S F, Gomes N. Amyotrophic lateral sclerosis (ALS): an overview of genetic and metabolic signaling mechanisms. CNS Neurol Disorders-Drug Targets. 2025;24(2):83–90.
Sathasivam S, Ince P, Shaw P. Apoptosis in amyotrophic lateral sclerosis: a review of the evidence. Neuropathol Appl Neurobiol. 2001;27(4):257–74.
Sathasivam S, Shaw PJ. Apoptosis in amyotrophic lateral sclerosis—what is the evidence? Lancet Neurol. 2005;4(8):500–9.
Saitoh Y, Takahashi Y. Riluzole for the treatment of amyotrophic lateral sclerosis. Neurodegenerative Disease Manage. 2020;10(6):343–55.
Fritz E, Izaurieta P, Weiss A, Mir FR, Rojas P, Gonzalez D, et al. Mutant SOD1-expressing astrocytes release toxic factors that trigger motoneuron death by inducing hyperexcitability. J Neurophysiol. 2013;109(11):2803–14.
Cho H, Shukla S. Role of Edaravone as a treatment option for patients with amyotrophic lateral sclerosis. Pharmaceuticals. 2020;14(1):29.
Yoshino H. Edaravone for the treatment of amyotrophic lateral sclerosis. Expert Rev Neurother. 2019;19(3):185–93.
Singh P, Belliveau P, Towle J, Neculau AE, Dima L. Edaravone oral suspension: a neuroprotective agent to treat amyotrophic lateral sclerosis. Am J Ther. 2024;31(3):e258–67.
Kutlubaev M. Promising approaches to the pathogenetic therapy of amyotrophic lateral sclerosis. Zhurnal Nevrologii I Psikhiatrii Imeni SS Korsakova. 2024;124(4):13–21.
Pressler M, Cooper P, Carter W, Mendelson A. ID: 205468 intrathecal Baclofen to improve functional status in ALS: A case report. Neuromodulation: Technol Neural Interface. 2023;26(4):S25.
McClelland IIIS, Bethoux FA, Boulis NM, Sutliff MH, Stough DK, Schwetz KM, et al. Intrathecal Baclofen for spasticity-related pain in amyotrophic lateral sclerosis: efficacy and factors associated with pain relief. Muscle Nerve: Official J Am Association Electrodiagn Med. 2008;37(3):396–8.
Reddy DS. Drug Therapy for Spasticity Disorders. Brody’s Human Pharmacology-E-Book: Brody’s Human Pharmacology-E-Book. 2024:207.
Kukkar A, Bali A, Singh N, Jaggi AS. Implications and mechanism of action of Gabapentin in neuropathic pain. Arch Pharm Res. 2013;36:237–51.
Everett EA, Brizzi K. 33 pain in amyotrophic lateral sclerosis. Pain. 2022:277.
Kwak S. Pain in amyotrophic lateral sclerosis: a narrative review. J Yeungnam Med Sci. 2022;39(3):181–9.
Dubovsky SL. Dextromethorphan/quinidine for pseudobulbar affect. 2014.
Sun Y, Benatar M, Mascías Cadavid J, Ennist D, Wicks P, Staats K, et al. ALSUntangled# 71: nuedexta. Amyotroph Lateral Scler Frontotemporal Degeneration. 2024;25(1–2):218–22.
Moretz D. New Drug Evaluation: Dextromethorphan/Quinidine (NUEDEXTA), capsules. 2024.
Jafari Z, Mahood Q, Hamson A. Riluzole for amyotrophic lateral sclerosis treatment. Can J Health Technol. 2023;3(7).
Miller RG, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane database of systematic reviews. 2012(3).
Watanabe K, Tanaka M, Yuki S, Hirai M, Yamamoto Y. How is Edaravone effective against acute ischemic stroke and amyotrophic lateral sclerosis? J Clin Biochem Nutr. 2018;62(1):20–38.
Bhandari R, Kuhad A. Edaravone: a new hope for deadly amyotrophic lateral sclerosis. Drugs Today (Barcelona Spain: 1998). 2018;54(6):349–60.
Cho H-J, Park J-M, Park J-S. Improved bulbar function in amyotrophic lateral sclerosis after nuedexta (dextromethorphan and quinidine) treatment. J Korean Neurol Association. 2019;37(2):171–3.
da Silva MN, da Silva JVB, da Fonsêca NF, Oshiro Junior JA, Dantas Medeiros AC. An overview of analytical methods for the identification and quantification of Baclofen. Curr Pharm Anal. 2023;19(5):353–70.
Kent CN, Park C, Lindsley CW. Classics in chemical neuroscience: Baclofen. ACS Chem Neurosci. 2020;11(12):1740–55.
Romito JW, Turner ER, Rosener JA, Coldiron L, Udipi A, Nohrn L, et al. Baclofen therapeutics, toxicity, and withdrawal: a narrative review. SAGE Open Med. 2021;9:20503121211022197.
Krause T, Gerbershagen M, Fiege M, Weisshorn R, Wappler F. Dantrolene–a review of its pharmacology, therapeutic use and new developments. Anaesthesia. 2004;59(4):364–73.
Dorst J, Ludolph AC, Huebers A. Disease-modifying and symptomatic treatment of amyotrophic lateral sclerosis. Ther Adv Neurol Disord. 2018;11:1756285617734734.
Chang C, Ramphul K, Amantadine. 2018.
Danysz W, Dekundy A, Scheschonka A, Riederer P. Amantadine: reappraisal of the timeless diamond-target updates and novel therapeutic potentials. J Neural Transmission (Vienna Austria: 1996). 2021;128(2):127–69.
Sills GJ. The mechanisms of action of Gabapentin and Pregabalin. Curr Opin Pharmacol. 2006;6(1):108–13.
McLean MJ. Gabapentin Epilepsia. 1995;36:S73–86.
Nicholson B. Gabapentin use in neuropathic pain syndromes. Acta Neurol Scand. 2000;101(6):359–71.
Wiffen PJ, McQuay HJ, Edwards J, Moore RA, Cochrane Pain P, Group SC. Gabapentin for acute and chronic pain. Cochrane Database Syst Reviews. 1996;2010(8).
Goslinga JA, Terrelonge M Jr, Bedlack R, Barkhaus P, Barnes B, Bertorini T, et al. ALSUntangled# 65: glucocorticoid corticosteroids. Amyotroph Lateral Scler Frontotemporal Degeneration. 2023;24(3–4):351–7.
Mullard A. Amylyx’s ALS therapy secures FDA approval, as regulatory flexibility Trumps underwhelming data. Nat Rev Drug Discovery. 2022;21(11):786.
Gordon PH. Amyotrophic lateral sclerosis: pathophysiology, diagnosis and management. CNS Drugs. 2011;25:1–15.
Weydt P, Weiss MD, Möller T, Carter GT. Neuro-inflammation as a therapeutic target in amyotrophic lateral sclerosis. Current opinion in investigational drugs (London, England: 2000). 2002;3(12):1720-4.
Corbett AH, Lim ML, Kashuba AD. Kaletra (lopinavir/ritonavir). Ann Pharmacother. 2002;36(7–8):1193–203.
Alfahad T, Nath A. Retroviruses and amyotrophic lateral sclerosis. Antiviral Res. 2013;99(2):180–7.
Schoergenhofer C, Jilma B, Stimpfl T, Karolyi M, Zoufaly A. Pharmacokinetics of lopinavir and Ritonavir in patients hospitalized with coronavirus disease 2019 (COVID-19). Ann Intern Med. 2020;173(8):670–2.
[Available from: National Center for Biotechnology Information. (2025). PubChem Compound Summary for CID 92727, Lopinavir. Retrieved May 26, 2025 from https://pubchem.ncbi.nlm.nih.gov/compound/Lopinavir
Liboux AL, Cachia JP, Kirkesseli S, Gautier JY, Guimart C, Montay G, et al. A comparison of the pharmacokinetics and tolerability of riluzole after repeat dose administration in healthy elderly and young volunteers. J Clin Pharmacol. 1999;39(5):480–6.
Wagner ML, Landis BE. Riluzole: a new agent for amyotrophic lateral sclerosis. Ann Pharmacother. 1997;31(6):738–44.
Jafari Z, Mahood Q, Hamson A. Riluzole for Amyotrophic Lateral Sclerosis Treatment: CADTH Health Technology Review. 2023.
Marquardt G, Seifert V. Use of intrathecal Baclofen for treatment of spasticity in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2002;72(2):275–6.
Boussicault L, Laffaire J, Schmitt P, Rinaudo P, Callizot N, Nabirotchkin S, et al. Combination of acamprosate and Baclofen (PXT864) as a potential new therapy for amyotrophic lateral sclerosis. J Neurosci Res. 2020;98(12):2435–50.
Granfors MT, Backman JT, Laitila J, Neuvonen PJ. Tizanidine is mainly metabolized by cytochrome p450 1A2 in vitro. Br J Clin Pharmacol. 2004;57(3):349–53.
Tse F, Jaffe J, Bhuta S. Pharmacokinetics of orally administered Tizanidine in healthy volunteers. Fundam Clin Pharmacol. 1987;1(6):479–88.
Brettschneider J, Kurent J, Ludolph A. Drug therapy for pain in amyotrophic lateral sclerosis or motor neuron disease. Cochrane Database Syst Reviews. 2013(6).
Wang Y-p. Ma M-y. Advance in clinical application of Dantrolene. Int J Anesthesiology Resusc. 2009;30:252–4.
Finsterer J. Familiar amyotrophic lateral sclerosis. New York: Nova Science Publishers, Inc.; 2006.
deVries T, Dentiste A, Handiwala L, Jacobs D. Bioavailability and pharmacokinetics of once-daily amantadine extended-release tablets in healthy volunteers: results from three randomized, crossover, open-label, phase 1 studies. Neurol Therapy. 2019;8:449–60.
Hauser RA, Pahwa R, Wargin WA, Souza-Prien CJ, McClure N, Johnson R, et al. Pharmacokinetics of ADS-5102 (amantadine) extended release capsules administered once daily at bedtime for the treatment of dyskinesia. Clin Pharmacokinet. 2019;58:77–88.
Lapshina MA, Shevtsova EF, Grigoriev VV, Aksinenko AY, Ustyugov AA, Steinberg DA, et al. New adamantane-containing Edaravone conjugates as potential neuroprotective agents for ALS treatments. Molecules. 2023;28(22):7567.
Miller R, Moore Dn, Gelinas D, Dronsky V, Mendoza M, Barohn R, et al. Phase III randomized trial of Gabapentin in patients with amyotrophic lateral sclerosis. Neurology. 2001;56(7):843–8.
Miller R, Moore D, Young L, Armon C, Barohn R, Bromberg M, et al. Placebo-controlled trial of Gabapentin in patients with amyotrophic lateral sclerosis. Neurology. 1996;47(6):1383–8.
Taylor CP, Gee NS, Su T-Z, Kocsis JD, Welty DF, Brown JP, et al. A summary of mechanistic hypotheses of Gabapentin Pharmacology. Epilepsy Res. 1998;29(3):233–49.
Alexander TH, Weisman MH, Derebery JM, Espeland MA, Gantz BJ, Gulya AJ, et al. Safety of high-dose corticosteroids for the treatment of autoimmune inner ear disease. Otology Neurotology. 2009;30(4):443–8.
Derendorf H, Hochhaus G, Meibohm B, Möllmann H, Barth J. Pharmacokinetics and pharmacodynamics of inhaled corticosteroids. J Allergy Clin Immunol. 1998;101(4):S440–6.
Czock D, Keller F, Rasche FM, Häussler U. Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005;44:61–98.
La Porte C, Colbers E, Bertz R, Voncken D, Wikstrom K, Boeree M, et al. Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with Rifampin in healthy volunteers. Antimicrob Agents Chemother. 2004;48(5):1553–60.
Kiser JJ, Gerber JG, Predhomme JA, Wolfe P, Flynn DM, Hoody DW. Drug/drug interaction between lopinavir/ritonavir and Rosuvastatin in healthy volunteers. JAIDS J Acquir Immune Defic Syndr. 2008;47(5):570–8.
Hill A, van der Lugt J, Sawyer W, Boffito M. How much Ritonavir is needed to boost protease inhibitors? Systematic review of 17 dose-ranging Pharmacokinetic trials. AIDS. 2009;23(17):2237–45.
Wang H, Guan L, Deng M. Recent progress of the genetics of amyotrophic lateral sclerosis and challenges of gene therapy. Front Neurosci. 2023;17:1170996.
Fang T, Je G, Pacut P, Keyhanian K, Gao J, Ghasemi M. Gene therapy in amyotrophic lateral sclerosis. Cells. 2022;11(13).
Zimmer AM, Pan YK, Chandrapalan T, Kwong RW, Perry SF. Loss-of-function approaches in comparative physiology: is there a future for knockdown experiments in the era of genome editing? J Exp Biol. 2019;222(7):jeb175737.
Han H. RNA interference to knock down gene expression. Disease Gene Identification: Methods Protocols. 2018:293–302.
Wang D, Gao G. State-of-the-art human gene therapy: part Ii. gene therapy strategies and applications. Discov Med. 2014;18(98):151.
Aquino-Jarquin G. CircRNA knockdown based on antisense strategies. Drug Discovery Today. 2024;29(8):104066.
Jakutis G, Stainier DY. Genotype–phenotype relationships in the context of transcriptional adaptation and genetic robustness. Annu Rev Genet. 2021;55(1):71–91.
Camlin NJ. Protein-targeting reverse genetic approaches: the future of oocyte and preimplantation embryo research. Mol Hum Reprod. 2025;31(2):gaaf008.
Brown RH, Al-Chalabi A. Amyotrophic lateral sclerosis. N Engl J Med. 2017;377(2):162–72.
Amado DA, Davidson BL. Gene therapy for ALS: A review. Mol Ther. 2021;29(12):3345–58.
Saha D, Paliwal B, Modak C, Mandal M, Dan S, Kumar P. Modern therapeutic approaches of neurological disorders: current insights and future perspectives. Evidence-Based Neurological Disorders: Jenny Stanford Publishing; 2024. pp. 383–422.
Kim J, Woo S, De Gusmao CM, Zhao B, Chin DH, DiDonato RL, et al. A framework for individualized splice-switching oligonucleotide therapy. Nature. 2023;619(7971):828–36.
Lin M, Hu X, Chang S, Chang Y, Bian W, Hu R, et al. Advances of antisense oligonucleotide technology in the treatment of hereditary neurodegenerative diseases. Evidence-Based Complement Altern Med. 2021;2021(1):6678422.
Lagier-Tourenne C, Baughn M, Rigo F, Sun S, Liu P, Li H-R, et al. Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. Proc Natl Acad Sci. 2013;110(47):E4530–9.
Cantara S, Simoncelli G, Ricci C. Antisense oligonucleotides (ASOs) in motor neuron diseases: a road to cure in light and shade. Int J Mol Sci. 2024;25(9):4809.
Bennett CF. Therapeutic antisense oligonucleotides are coming of age. Annu Rev Med. 2019;70(1):307–21.
McDowall S, Aung-Htut M, Wilton S, Li D. Antisense oligonucleotides and their applications in rare neurological diseases. Front NeuroSci. 2024;18:1414658.
Cappella M, Ciotti C, Cohen-Tannoudji M, Biferi MG. Gene therapy for ALS-A perspective. Int J Mol Sci. 2019;20(18).
Ly CV, Miller TM. Emerging antisense oligonucleotide and viral therapies for amyotrophic lateral sclerosis. Curr Opin Neurol. 2018;31(5):648–54.
Bosscher H. Pressure-volume relationships in the spinal Canal and potential neurological complications after epidural fluid injections. Front Pain Res. 2022;3:884277.
Khan SI, Ahmed N, Ahsan K, Abbasi M, Maugeri R, Chowdhury D, et al. An insight into the prospects and drawbacks of stem cell therapy for spinal cord injuries: ongoing trials and future directions. Brain Sci. 2023;13(12):1697.
Chan CH, Desai SR, Hwang NC. Cerebrospinal fluid drains: risks in contemporary clinical practice. J Cardiothorac Vasc Anesth. 2022;36(8):2685–99.
Chen S, Sayana P, Zhang X, Le W. Genetics of amyotrophic lateral sclerosis: an update. Mol Neurodegener. 2013;8:28.
Abel O, Powell JF, Andersen PM, Al-Chalabi A. ALSoD: A user-friendly online bioinformatics tool for amyotrophic lateral sclerosis genetics. Hum Mutat. 2012;33(9):1345–51.
Ekhtiari Bidhendi E, Bergh J, Zetterström P, Forsberg K, Pakkenberg B, Andersen PM, et al. Mutant superoxide dismutase aggregates from human spinal cord transmit amyotrophic lateral sclerosis. Acta Neuropathol. 2018;136(6):939–53.
Miller TM, Pestronk A, David W, Rothstein J, Simpson E, Appel SH, et al. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 Familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol. 2013;12(5):435–42.
Miller T, Cudkowicz M, Shaw PJ, Andersen PM, Atassi N, Bucelli RC, et al. Phase 1–2 trial of antisense oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 2020;383(2):109–19.
Miller TM, Cudkowicz ME, Genge A, Shaw PJ, Sobue G, Bucelli RC, et al. Trial of antisense oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 2022;387(12):1099–110.
Donnelly CJ, Zhang PW, Pham JT, Haeusler AR, Mistry NA, Vidensky S, et al. RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention. Neuron. 2013;80(2):415–28.
van den Berg LH, Rothstein JD, Shaw PJ, Babu S, Benatar M, Bucelli RC, et al. Safety, tolerability, and pharmacokinetics of antisense oligonucleotide BIIB078 in adults with C9orf72-associated amyotrophic lateral sclerosis: a phase 1, randomised, double blinded, placebo-controlled, multiple ascending dose study. Lancet Neurol. 2024;23(9):901–12.
Sproviero W, Shatunov A, Stahl D, Shoai M, van Rheenen W, Jones AR, et al. ATXN2 trinucleotide repeat length correlates with risk of ALS. Neurobiol Aging. 2017;51:178. e1-. e9.
Elden AC, Kim H-J, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature. 2010;466(7310):1069–75.
Tian Y, Heinsinger N, Hu Y, Lim U-M, Wang Y, Fernandis AZ, et al. Deciphering the interactome of Ataxin-2 and TDP-43 in iPSC-derived neurons for potential ALS targets. PLoS ONE. 2024;19(12):e0308428.
Ling JP, Pletnikova O, Troncoso JC, Wong PC. TDP-43 repression of nonconserved cryptic exons is compromised in ALS-FTD. Science. 2015;349(6248):650–5.
Mathis S, Le Masson G. RNA-Targeted therapies and amyotrophic lateral sclerosis. Biomedicines. 2018;6(1).
Gaj T, Ojala DS, Ekman FK, Byrne LC, Limsirichai P, Schaffer DV. In vivo genome editing improves motor function and extends survival in a mouse model of ALS. Sci Adv. 2017;3(12):eaar3952.
Lim CKW, Gapinske M, Brooks AK, Woods WS, Powell JE, Zeballos CM, et al. Treatment of a mouse model of ALS by in vivo base editing. Mol Ther. 2020;28(4):1177–89.
Duan W, Guo M, Yi L, Liu Y, Li Z, Ma Y, et al. The deletion of mutant SOD1 via CRISPR/Cas9/sgRNA prolongs survival in an amyotrophic lateral sclerosis mouse model. Gene Ther. 2020;27(3):157–69.
Kim BW, Ryu J, Jeong YE, Kim J, Martin LJ. Human motor neurons with SOD1-G93A mutation generated from CRISPR/Cas9 gene-edited iPSCs develop pathological features of amyotrophic lateral sclerosis. Front Cell Neurosci. 2020;14:604171.
Guo C, Ma X, Gao F, Guo Y. Off-target effects in CRISPR/Cas9 gene editing. Front Bioeng Biotechnol. 2023;11:1143157.
Cetin B, Erendor F, Eksi YE, Sanlioglu AD, Sanlioglu S. Advancing CRISPR genome editing into gene therapy clinical trials: progress and future prospects. Expert Rev Mol Med. 2025:1–96.
Dai W-J, Zhu L-Y, Yan Z-Y, Xu Y, Wang Q-L, Lu X-J. CRISPR-Cas9 for in vivo gene therapy: promise and hurdles. Mol Therapy Nucleic Acids. 2016;5.
Eski N, Asif H, Crespo J, Bayar Y. Exploring the role of CRISPR-Cas9 in genetic engineering: Advancements, Applications, and ethical issue. Lond J Interdisciplinary Sci. 2025;4:38–51.
Stoica L, Sena-Esteves M. Adeno associated viral vector delivered RNAi for gene therapy of SOD1 amyotrophic lateral sclerosis. Front Mol Neurosci. 2016;9:56.
Hocquemiller M, Giersch L, Audrain M, Parker S, Cartier N. Adeno-Associated Virus-Based gene therapy for CNS diseases. Hum Gene Ther. 2016;27(7):478–96.
Li J-H, Liu J-L, Zhang K-K, Chen L-J, Xu J-T, Xie X-L. The adverse effects of prenatal METH exposure on the offspring: a review. Front Pharmacol. 2021;12:715176.
Gouel F, Rolland AS, Devedjian JC, Burnouf T, Devos D. Past and future of neurotrophic growth factors therapies in ALS: from single neurotrophic growth factor to stem cells and human platelet lysates. Front Neurol. 2019;10:835.
Lim ST, Airavaara M, Harvey BK. Viral vectors for neurotrophic factor delivery: a gene therapy approach for neurodegenerative diseases of the CNS. Pharmacol Res. 2010;61(1):14–26.
Cheng W, Huang J, Fu XQ, Tian WY, Zeng PM, Li Y, et al. Intrathecal delivery of AAV-NDNF ameliorates disease progression of ALS mice. Mol Ther. 2023;31(11):3277–89.
Costa-Verdera H, Unzu C, Valeri E, Adriouch S, González Aseguinolaza G, Mingozzi F, et al. Understanding and tackling immune responses to adeno-associated viral vectors. Hum Gene Ther. 2023;34(17–18):836–52.
Chamberlain K, Riyad JM, Weber T. Expressing transgenes that exceed the packaging capacity of adeno-associated virus capsids. Hum Gene Therapy Methods. 2016;27(1):1–12.
Gardin A, Ronzitti G. Current limitations of gene therapy for rare pediatric diseases: lessons learned from clinical experience with AAV vectors. Archives De Pédiatrie. 2023;30(8):S846–52.
Fu X, Suo H, Zhang J, Chen D. Machine-learning-guided directed evolution for AAV capsid engineering. Curr Pharm Design. 2024;30(11):811–24.
Poulin-Brière A, Rezaei E, Pozzi S. Antibody-Based therapeutic interventions for amyotrophic lateral sclerosis: A systematic literature review. Front Neurosci. 2021;15:790114.
Cykowski MD, Dickson DW, Powell SZ, Arumanayagam AS, Rivera AL, Appel SH. Dipeptide repeat (DPR) pathology in the skeletal muscle of ALS patients with C9ORF72 repeat expansion. Acta Neuropathol. 2019;138(4):667–70.
Nguyen L, Montrasio F, Pattamatta A, Tusi SK, Bardhi O, Meyer KD, et al. Antibody therapy targeting RAN proteins rescues C9 ALS/FTD phenotypes in C9orf72 mouse model. Neuron. 2020;105(4):645–e6211.
Steiner JP, Bachani M, Malik N, DeMarino C, Li W, Sampson K, et al. Human endogenous retrovirus K envelope in spinal fluid of amyotrophic lateral sclerosis is toxic. Ann Neurol. 2022;92(4):545–61.
Halcrow PW, Quansah DN, Kumar N, Steiner JP, Nath A, Geiger JD. HERV-K (HML-2) envelope protein induces mitochondrial depolarization and neurotoxicity via endolysosome iron dyshomeostasis. J Neurosci. 2024;44(14).
Garcia-Montojo M, Simula ER, Fathi S, McMahan C, Ghosal A, Berry JD, et al. Antibody response to HML‐2 May be protective in amyotrophic lateral sclerosis. Ann Neurol. 2022;92(5):782–92.
Perrin S, Ladha S, Maragakis N, Rivner MH, Katz J, Genge A, et al. Safety and tolerability of Tegoprubart in patients with amyotrophic lateral sclerosis: A phase 2A clinical trial. PLoS Med. 2024;21(10):e1004469.
Mu L, Dong R, Guo B. Biomaterials-based cell therapy for myocardial tissue regeneration. Adv Healthc Mater. 2023;12(10):2202699.
Rajabi M, Shafaeibajestan S, Asadpour S, Alyari G, Taei N, Kohkalani M, et al. Primary progressive multiple sclerosis: new therapeutic approaches. Neuropsychopharmacol Rep. 2025;45(3):e70039.
Lecour S, Bøtker HE, Condorelli G, Davidson SM, Garcia-Dorado D, Engel FB, et al. ESC working group cellular biology of the heart: position paper: improving the preclinical assessment of novel cardioprotective therapies. Cardiovascular Res. 2014;104(3):399–411.
Lau AN, Goodwin M, Kim CF, Weiss DJ. Stem cells and regenerative medicine in lung biology and diseases. Mol Ther. 2012;20(6):1116–30.
Yavarpour-Bali H, Nakhaei‐Nejad M, Yazdi A, Ghasemi‐Kasman M. Direct conversion of somatic cells towards oligodendroglial lineage cells: A novel strategy for enhancement of Myelin repair. J Cell Physiol. 2020;235(3):2023–36.
Raoufinia R, Arabnezhad A, Keyhanvar N, Abdyazdani N, Saburi E, Naseri N, et al. Leveraging stem cells to combat hepatitis: a comprehensive review of recent studies. Mol Biol Rep. 2024;51(1):459.
Raoufinia R, Rahimi HR, Saburi E, Moghbeli M. Advances and challenges of the cell-based therapies among diabetic patients. J Translational Med. 2024;22(1):435.
Memarpour S, Raoufinia R, Saburi E, Razavi MS, Attaran M, Fakoor F, et al. The future of diabetic wound healing: unveiling the potential of mesenchymal stem cell and exosomes therapy. Am J Stem Cells. 2024;13(2):87–100.
Raoufinia R, Rahimi Hr, Keyhanvar N, Moghbeli M, Abdyazdani N, Rostami M, et al. Advances in treatments for epidermolysis Bullosa (EB): emphasis on stem Cell-Based therapy. Stem Cell Reviews Rep. 2024;20(5):1200–12.
Salimi Z, Rostami M, Milasi YE, Mafi A, Raoufinia R, Kiani A, et al. Unfolded protein response signaling in hepatic stem cell activation in liver fibrosis. Curr Protein Pept Sci. 2024;25(1):59–70.
Lin S-L. Concise review: Deciphering the mechanism behind induced pluripotent stem cell generation. Stem Cells. 2011;29(11):1645–9.
Puri MC, Nagy A. Concise review: embryonic stem cells versus induced pluripotent stem cells: the game is on. Stem Cells. 2012;30(1):10–4.
Pototskaya OY, Shevchenko K. Comparative characteristics of human stem cells. Морфологія= Morphologia. 2022;16(2):6–21.
Wang L, Liu G, Zheng L, Long H, Liu Y. A new era of gene and cell therapy for cancer: A narrative review. Annals Translational Med. 2023;11(9):321.
Sari BA, Zahra AT, Tasti GP, Maritska Z. Healing the fundamental unit of heredity (gene therapy): current perspective and what the future holds. Mol Cell Biomedical Sci. 2021;5(2):62–7.
Young RM, Engel NW, Uslu U, Wellhausen N, June CH. Next-generation CAR T-cell therapies. Cancer Discov. 2022;12(7):1625–33.
Sun D, Shi X, Li S, Wang X, Yang X, Wan M. CAR–T cell therapy: A breakthrough in traditional cancer treatment strategies. Mol Med Rep. 2024;29(3):47.
Rathi D, Patel N, Satapathy T. Chimeric antigen receptor T-Cells (CAR T-Cells): an engineered targeted therapy for treatment of cancer. J Drug Delivery Ther. 2024;14(9).
Mody H, Sutaria DS, Miles D. Clinical Pharmacology considerations for the Off-the‐Shelf allogeneic cell therapies. Clin Pharmacol Ther. 2024;115(6):1233–50.
Dhakal B, Chhabra S, Savani BN, Hamadani M. Promise and pitfalls of allogeneic chimeric antigen receptor therapy in plasma cell and lymphoid malignancies. Br J Haematol. 2022;197(1):28–40.
Sasu BJ, Lauron EJ, Schulz T, Cheng H-Y, Sommer C. Allogeneic CAR T cell therapy for cancer. Annual Rev Cancer Biology. 2024;8.
Martínez Bedoya D, Dutoit V, Migliorini D. Allogeneic CAR T cells: an alternative to overcome challenges of CAR T cell therapy in glioblastoma. Front Immunol. 2021;12:640082.
Bruno A, Milillo C, Anaclerio F, Buccolini C, Dell’Elice A, Angilletta I, et al. Perinatal tissue-derived stem cells: an emerging therapeutic strategy for challenging neurodegenerative diseases. Int J Mol Sci. 2024;25(2):976.
Je G, Keyhanian K, Ghasemi M. Overview of stem cells therapy in amyotrophic lateral sclerosis. Neurol Res. 2021;43(8):616–32.
Du H, Huo Z, Chen Y, Zhao Z, Meng F, Wang X, et al. Induced pluripotent stem cells and their applications in amyotrophic lateral sclerosis. Cells. 2023;12(6):971.
Mazzini L, De Marchi F, Buzanska L, Follenzi A, Glover JC, Gelati M, et al. Current status and new avenues of stem cell-based preclinical and therapeutic approaches in amyotrophic lateral sclerosis. Expert Opin Biol Ther. 2024;24(9):933–54.
Karpe Y, Chen Z, Li X-J. Stem cell models and gene targeting for human motor neuron diseases. Pharmaceuticals. 2021;14(6):565.
Gomez AM, Staff NP, Ekker SC. 482 translational gene editing strategies for Understanding and treating CHCHD10-associated amyotrophic lateral sclerosis (ALS). J Clin Translational Sci. 2025;9(s1):143.
Patmanathan SN, Gnanasegaran N, Lim MN, Husaini R, Fakiruddin KS, Zakaria Z. CRISPR/Cas9 in stem cell research: current application and future perspective. Curr Stem Cell Res Therapy. 2018;13(8):632–44.
Liu B, Li M, Zhang L, Chen Z, Lu P. Motor neuron replacement therapy for amyotrophic lateral sclerosis. Neural Regeneration Res. 2022;17(8):1633–9.
Lunn JS, Sakowski SA, Feldman EL. Concise review: stem cell therapies for amyotrophic lateral sclerosis: recent advances and prospects for the future. Stem Cells. 2014;32(5):1099–109.
Lu L, Deng Y, Xu R. Current potential therapeutics of amyotrophic lateral sclerosis. Front Neurol. 2024;15:1402962.
Khalid MU, Masroor T. The promise of stem cells in amyotrophic lateral sclerosis: a review of clinical trials. JPMA J Pakistan Med Association. 2023;73(2):S138–42.
Frawley L, Taylor NT, Sivills O, McPhillamy E, To TD, Wu Y, et al. Stem cell therapy for the treatment of amyotrophic lateral sclerosis: comparison of the efficacy of mesenchymal stem cells, neural stem cells, and induced pluripotent stem cells. Biomedicines. 2024;13(1):35.
Rae SB, DeGiorgio CM. Ethical issues in fetal tissue transplants. Linacre Q. 1991;58(3):12–32.
Mazzini L, Vescovi A, Cantello R, Gelati M, Vercelli A. Stem cells therapy for ALS. Expert Opin Biol Ther. 2016;16(2):187–99.
Guillot PV, Gotherstrom C, Chan J, Kurata H, Fisk NM. Human first-trimester fetal MSC express pluripotency markers and grow faster and have longer telomeres than adult MSC. Stem Cells. 2007;25(3):646–54.
Lescaudron L, Naveilhan P, Neveu I. The use of stem cells in regenerative medicine for parkinson’s and huntington’s diseases. Curr Med Chem. 2012;19(35):6018–35.
Cave JW, Wang M, Baker H. Adult subventricular zone neural stem cells as a potential source of dopaminergic replacement neurons. Front NeuroSci. 2014;8:16.
Kooreman NG, Wu JC. Tumorigenicity of pluripotent stem cells: biological insights from molecular imaging. J Royal Soc Interface. 2010;7(suppl6):S753–63.
Su Z, Dong H, Fang X, Zhang W, Duan H. Frontier progress and translational challenges of pluripotent differentiation of stem cells. Front Genet. 2025;16:1583391.
Nishio M, Nakahara M, Yuo A, Saeki K. Human pluripotent stem cells: towards therapeutic development for the treatment of lifestyle diseases. World J Stem Cells. 2016;8(2):56.
Mohseni R, Hamidieh AA, Verdi J, Shoae-Hassani A. Safe transplantation of pluripotent stem cell by preventing teratoma formation. Stem Cell Res Therapy. 2014;4(6):104172.
Liu SP, Fu RH, Huang YC, Chen SY, Chien YJ, Hsu CY, et al. Induced pluripotent stem (iPS) cell research overview. Cell Transplant. 2011;20(1):15–9.
Dupuis V, Oltra E. Methods to produce induced pluripotent stem cell-derived mesenchymal stem cells: mesenchymal stem cells from induced pluripotent stem cells. World J Stem Cells. 2021;13(8):1094–111.
Crippa V, Sau D, Rusmini P, Boncoraglio A, Onesto E, Bolzoni E, et al. The small heat shock protein B8 (HspB8) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS). Hum Mol Genet. 2010;19(17):3440–56.
Riley J, Glass J, Feldman EL, Polak M, Bordeau J, Federici T, et al. Intraspinal stem cell transplantation in amyotrophic lateral sclerosis: a phase I trial, cervical microinjection, and final surgical safety outcomes. Neurosurgery. 2014;74(1):77–87.
Glass JD, Boulis NM, Johe K, Rutkove SB, Federici T, Polak M, et al. Lumbar intraspinal injection of neural stem cells in patients with amyotrophic lateral sclerosis: results of a phase I trial in 12 patients. Stem Cells. 2012;30(6):1144–51.
Nowicka N, Juranek J, Juranek JK, Wojtkiewicz J. Risk factors and emerging therapies in amyotrophic lateral sclerosis. Int J Mol Sci. 2019;20(11):2616.
Chavda VP, Patel C, Modh D, Ertas YN, Sonak SS, Munshi NK, et al. Therapeutic approaches to amyotrophic lateral sclerosis from the lab to the clinic. Curr Drug Metab. 2022;23(3):200–22.
Brenner D, Freischmidt A. Update on genetics of amyotrophic lateral sclerosis. Curr Opin Neurol. 2022;35(5):672–7.
Yun Y, Ha Y. CRISPR/Cas9-mediated gene correction to understand ALS. Int J Mol Sci. 2020;21(11):3801.
Shi Y, Zhao Y, Lu L, Gao Q, Yu D, Sun M. CRISPR/Cas9: implication for modeling and therapy of amyotrophic lateral sclerosis. Front NeuroSci. 2023;17:1223777.
Wang JY, Doudna JA. CRISPR technology: A decade of genome editing is only the beginning. Science. 2023;379(6629):eadd8643.
Kumar R, Bargoti T, Sengar S, Singh D, Nain V. A decade of genome editing: comparative review of Zfn, Talen, and Crispr/Cas9. Int J Innovative Sci Res Technol. 2025;10(4):3708–17.
Cudkowicz ME, Lindborg SR, Goyal NA, Miller RG, Burford MJ, Berry JD, et al. A randomized placebo-controlled phase 3 study of mesenchymal stem cells induced to secrete high levels of neurotrophic factors in amyotrophic lateral sclerosis. Muscle Nerve. 2022;65(3):291–302.
Aricha R, Abramov N, Semo J, Kaspi H, Lebovits C, Kern R. MSC-NTF cell immunomodulation: effects on T and B regulatory cells (790). Neurology. 2020;94(15supplement):790.
Morata-Tarifa C, Azkona G, Glass J, Mazzini L, Sanchez-Pernaute R. Looking backward to move forward: a meta-analysis of stem cell therapy in amyotrophic lateral sclerosis. Npj Regenerative Med. 2021;6(1):20.
Aljabri A, Halawani A, Bin Lajdam G, Labban S, Alshehri S, Felemban R. The safety and efficacy of stem cell therapy as an emerging therapy for ALS: A systematic review of controlled clinical trials. Front Neurol. 2021;Volume 12–2021.
Goutman SA, Savelieff MG, Sakowski SA, Feldman EL. Stem cell treatments for amyotrophic lateral sclerosis: a critical overview of early phase trials. Expert Opin Investig Drugs. 2019;28(6):525–43.
Agrawal S, Vaidya S, Patel J, Jirvankar P, Gurjar P. Challenges and pathways in regulating Next-Gen biological therapies. Current pharmaceutical biotechnology.
Shah V, Al-Shehab U, Patel K, King A. Mesenchymal Stem Cell Therapy for Amyotrophic Lateral Sclerosis. 2023.
Janson C, Ramesh T, During M, Leone P, Heywood J. Human intrathecal transplantation of peripheral blood stem cells in amyotrophic lateral sclerosis. J Hematotherapy Stem Cell Res. 2001;10(6):913–5.
Mazzini L, Fagioli F, Boccaletti R, Mareschi K, Oliveri G, Olivieri C, et al. Stem cell therapy in amyotrophic lateral sclerosis: a methodological approach in humans. Amyotroph Lateral Scler Other Motor Neuron Disorders. 2003;4(3):158–61.
Mazzini L, Mareschi K, Ferrero I, Vassallo E, Oliveri G, Boccaletti R, et al. Autologous mesenchymal stem cells: clinical applications in amyotrophic lateral sclerosis. Neurol Res. 2006;28(5):523–6.
Cashman E, Skinner LJ, Timon C. Thyroid swelling: an unusual presentation of a cervical sympathetic chain Schwannoma. Medscape J Med. 2008;10(8):201.
Deda H, Inci MC, Kürekçi AE, Sav A, Kayihan K, Ozgün E, et al. Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation: a 1-year follow-up. Cytotherapy. 2009;11(1):18–25.
Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, et al. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2010;67(10):1187–94.
Mazzini L, Ferrero I, Luparello V, Rustichelli D, Gunetti M, Mareschi K, et al. Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A phase I clinical trial. Exp Neurol. 2010;223(1):229–37.
Sharma AK, Sane HM, Paranjape AA, Gokulchandran N, Nagrajan A, D’sa M, et al. The effect of autologous bone marrow mononuclear cell transplantation on the survival duration in amyotrophic lateral Sclerosis-a retrospective controlled study. Am J Stem Cells. 2015;4(1):50.
Mazzini L, Gelati M, Profico DC, Sgaravizzi G, Projetti Pensi M, Muzi G, et al. Human neural stem cell transplantation in ALS: initial results from a phase I trial. J Translational Med. 2015;13:1–16.
Rushkevich YN, Kosmacheva S, Zabrodets G, Ignatenko S, Goncharova N, Severin I, et al. The use of autologous mesenchymal stem cells for cell therapy of patients with amyotrophic lateral sclerosis in Belarus. Bull Exp Biol Med. 2015;159(4):576–81.
Oh K-W, Moon C, Kim HY, Oh S-i, Park J, Lee JH, et al. Phase I trial of repeated intrathecal autologous bone marrow-derived mesenchymal stromal cells in amyotrophic lateral sclerosis. Stem Cells Translational Med. 2015;4(6):590–7.
Petrou P, Gothelf Y, Argov Z, Gotkine M, Levy YS, Kassis I, et al. Safety and clinical effects of mesenchymal stem cells secreting neurotrophic factor transplantation in patients with amyotrophic lateral sclerosis: results of phase 1/2 and 2a clinical trials. JAMA Neurol. 2016;73(3):337–44.
Kuzma-Kozakiewicz M, Marchel A, Kaminska A, Gawel M, Sznajder J, Figiel-Dabrowska A, et al. Intraspinal transplantation of the adipose Tissue-Derived regenerative cells in amyotrophic lateral sclerosis in accordance with the current experts’ recommendations: choosing optimal monitoring tools. Stem Cells Int. 2018;2018(1):4392017.
Berry JD, Cudkowicz ME, Windebank AJ, Staff NP, Owegi M, Nicholson K, et al. NurOwn, phase 2, randomized, clinical trial in patients with ALS: safety, clinical, and biomarker results. Neurology. 2019;93(24):e2294–305.
Geijo-Barrientos E, Pastore-Olmedo C, De Mingo P, Blanquer M, Gómez Espuch J, Iniesta F, et al. Intramuscular injection of bone marrow stem cells in amyotrophic lateral sclerosis patients: a randomized clinical trial. Front NeuroSci. 2020;14:195.
Petrou P, Kassis I, Yaghmour NE, Ginzberg A, Karussis D. A phase II clinical trial with repeated intrathecal injections of autologous mesenchymal stem cells in patients with amyotrophic lateral sclerosis. Front Bioscience-Landmark. 2021;26(10):693–706.
Tavakol-Afshari J, Boroumand AR, Farkhad NK, Moghadam AA, Sahab-Negah S, Gorji A. Safety and efficacy of bone marrow derived-mesenchymal stem cells transplantation in patients with amyotrophic lateral sclerosis. Regenerative Therapy. 2021;18:268–74.
Baloh RH, Johnson JP, Avalos P, Allred P, Svendsen S, Gowing G, et al. Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial. Nat Med. 2022;28(9):1813–22.
Gotkine M, Caraco Y, Lerner Y, Blotnick S, Wanounou M, Slutsky SG, et al. Safety and efficacy of first-in-man intrathecal injection of human astrocytes (AstroRx®) in ALS patients: phase I/IIa clinical trial results. J Translational Med. 2023;21(1):122.
Yamashita T, Nakano Y, Sasaki R, Tadokoro K, Omote Y, Yunoki T, et al. Safety and clinical effects of a muse cell-based product in patients with amyotrophic lateral sclerosis: results of a phase 2 clinical trial. Cell Transplant. 2023;32:09636897231214370.
Staff N, Oskarsson B, Muzyka I, Madigan N, Mester C, Figdore D, et al. editors. Results from a phase 2 clinical trial of repeated intrathecal autologous Adipose-derived MSCs in ALS (S5. 004). Lippincott Williams & Wilkins Hagerstown, MD; 2024.
Alkhazaali-Ali Z, Sahab-Negah S, Boroumand AR, Farkhad NK, Khodadoust MA, Tavakol-Afshari J. Evaluation of the safety and efficacy of repeated mesenchymal stem cell transplantations in ALS patients by investigating patients’ specific immunological and biochemical biomarkers. Diseases. 2024;12(5):99.
Alkhazaali-Ali Z, Sahab-Negah S, Boroumand AR, Farkhad NK, Khodadoust MA, Ganjali R et al. Evaluation of Safety and Efficacy of Repeated Mesenchymal Stem Cell Transplantation in Patients with Amyotrophic Lateral Sclerosis (ALS) by Investigating Patient’s Specific microRNAs as Novel Biomarkers: A Clinical Trial Study. Curr Stem Cell Res Ther. 2025.