Genetic and Mechanistic Insights Inform Amyotrophic Lateral Sclerosis Treatment and Symptomatic Management: Current and Emerging Therapeutics and Clinical Trial Design Considerations

Feldman EL, et al. Amyotrophic lateral sclerosis. Lancet. 2022;400(10360):1363–80.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vignaroli F, et al. The need for biomarkers in the ALS-FTD spectrum: a clinical point of view on the role of proteomics. Proteomes. 2023. https://doi.org/10.3390/proteomes11010001.

Article  PubMed  PubMed Central  Google Scholar 

Larson TC, et al. Causes of death among United States decedents with ALS: an eye toward delaying mortality. Ann Clin Transl Neurol. 2023;10(5):757–64.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mehta P, et al. Prevalence of amyotrophic lateral sclerosis in the United States. Amyotroph Lateral Scler Frontotemporal Degener. 2018;2023:1–7.

Google Scholar 

Mitsumoto H, Kasarskis EJ, Simmons Z. Hastening the diagnosis of amyotrophic lateral sclerosis. Neurology. 2022;99(2):60–8.

Article  CAS  PubMed  Google Scholar 

Ryan M, et al. Lifetime risk and heritability of amyotrophic lateral sclerosis. JAMA Neurol. 2019;76(11):1367–74.

Article  PubMed  PubMed Central  Google Scholar 

Goutman SA, et al. Emerging insights into the complex genetics and pathophysiology of amyotrophic lateral sclerosis. Lancet Neurol. 2022;21(5):465–79.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mead RJ, et al. Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation. Nat Rev Drug Discov. 2023;22(3):185–212.

Article  CAS  PubMed  Google Scholar 

Umoh ME, et al. A proteomic network approach across the ALS-FTD disease spectrum resolves clinical phenotypes and genetic vulnerability in human brain. EMBO Mol Med. 2018;10(1):48–62.

Article  CAS  PubMed  Google Scholar 

Benatar M, Robertson J, Andersen PM. Amyotrophic lateral sclerosis caused by SOD1 variants: from genetic discovery to disease prevention. Lancet Neurol. 2025;24(1):77–86.

Article  CAS  PubMed  Google Scholar 

Marrone L, et al. Fus pathology in ALS is linked to alterations in multiple ALS-associated proteins and rescued by drugs stimulating autophagy. Acta Neuropathol. 2019;138(1):67–84.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Blokhuis AM, et al. Protein aggregation in amyotrophic lateral sclerosis. Acta Neuropathol. 2013;125(6):777–94.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Adams J, Lee M, Peng W. Critical review of complementary and alternative medicine use in amyotrophic lateral sclerosis: prevalence and users’ profile, decision-making, information seeking, and disclosure in the face of a lack of efficacy. Neurodegener Dis. 2018;18(4):225–32.

Article  PubMed  Google Scholar 

Goutman SA, et al. ALS identified: two-year findings from a sponsored ALS genetic testing program. Ann Clin Transl Neurol. 2024;11(8):2201–11.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dharmadasa T, et al. Genetic testing in motor neurone disease. Pract Neurol. 2022;22(2):107–16.

Article  PubMed  PubMed Central  Google Scholar 

Bosco DA, et al. Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS. Nat Neurosci. 2010;13(11):1396–403.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang W, et al. Role of neuroinflammation in neurodegeneration development. Signal Transduct Target Ther. 2023;8(1): 267.

Article  PubMed  PubMed Central  Google Scholar 

Smith RA. Antisense oligonucleotide therapy for neurodegenerative disease. J Clin Invest. 2006;116(8):2290–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ludolph AC, et al. Guidelines for preclinical animal research in ALS/MND: a consensus meeting. Amyotroph Lateral Scler. 2010;11(1–2):38–45.

Article  PubMed  Google Scholar 

Babic Leko M, et al. Molecular mechanisms of neurodegeneration related to C9orf72 hexanucleotide repeat expansion. Behav Neurol. 2019;2019:2909168.

Article  PubMed  PubMed Central  Google Scholar 

Hao Z, et al. Role of the C9ORF72 gene in the pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia. Neurosci Bull. 2020;36(9):1057–70.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ruffo P, Traynor BJ, Conforti FL. Advancements in genetic research and RNA therapy strategies for amyotrophic lateral sclerosis (ALS): current progress and future prospects. J Neurol. 2025;272(3):233.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Moens TG, et al. Amyotrophic lateral sclerosis caused by FUS mutations: advances with broad implications. Lancet Neurol. 2025;24(2):166–78.

Article  CAS  PubMed  Google Scholar 

Pozzi L, et al. TBK1 mutations in Italian patients with amyotrophic lateral sclerosis: genetic and functional characterisation. J Neurol Neurosurg Psychiatry. 2017;88(10):869–75.

Article  PubMed  Google Scholar 

Pensato V, et al. Exploring NEK1 genetic variability in Italian amyotrophic lateral sclerosis patients. J Neurol. 2025;272(7):469.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Riva N, et al. NEK1 variants in a cohort of Italian patients with amyotrophic lateral sclerosis. Front Neurosci. 2022;16: 833051.

Article  PubMed  PubMed Central  Google Scholar 

Amyotrophic lateral sclerosis: developing drugs for treatment guidance for industry. Food and Drug Administration. 2019.

van Eijk RPA, et al. Critical design considerations for time-to-event endpoints in amyotrophic lateral sclerosis clinical trials. J Neurol Neurosurg Psychiatry. 2019;90(12):1331–7.

PubMed  Google Scholar 

Marin B, et al. Non-self-sufficiency as a primary outcome measure in ALS trials. Amyotroph Lateral Scler Frontotemporal Degener. 2015;17(1–2):77–84.

PubMed  Google Scholar 

Cedarbaum JM, et al. The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci. 1999;169(1–2):13–21.

Article  CAS  PubMed  Google Scholar 

Atassi N, et al. The PRO-ACT database: design, initial analyses, and predictive features. Neurology. 2014;83(19):1719–25.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Labra J, et al. Rate of disease progression: a prognostic biomarker in ALS. J Neurol Neurosurg Psychiatry. 2016;87(6):628–32.

Article  PubMed  Google Scholar 

Kimura F, et al. Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS. Neurology. 2006;66(2):265–7.

Article  CAS 

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