Updates from the fray: rational off-label and over-the-counter prescribing in amyotrophic lateral sclerosis

Authors

DOI:

https://doi.org/10.17161/rrnmf.v2i1.14789

Keywords:

Amyotrophic lateral sclerosis, Clinical trials, Review, Off-label prescribing

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a terminal condition, which is increasing in incidence. Therapeutic interventions have enjoyed limited success. However, research is progressing, with some promising drug candidates emerging. Patients cannot always wait for the results of large trials. The general practitioner has a central role in management of ALS.

Objective: To review and summarise available evidence evaluating the disease-modifying and life-extending potential of approved medications available off-label or over the counter. To inform doctors and patients of updates in the field and assist their decision-making.

Discussion: Three experimental candidates were deemed to have a reasonable likelihood of efficacy, and doses/routes of administration were clarified. Possibilities for novel therapies were outlined, and the importance of research support was highlighted.

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References

Deloitte Access Economics. Economic analysis of motor neurone disease in Australia. Canberra: Deloitte Access Economics; 2015.

Lau F, Brennan F, Gardiner M. Multidisciplinary management of motor neurone disease. Australian Journal for General Practitioners 2018; 47(9): 593-597. DOI: 10.31128/AJGP-02-18-4495

Fornai F, Longone P, Cafaro L, et al. Lithium delays progression of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 2008; 105(6): 2052-7. DOI: 10.1073/pnas.0708022105

Cudkowicz M, Bozik ME, Ingersoll EW, et al. The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis. Nat Med 2011; 17(12): 1652-6. DOI: 10.1038/nm.2579

McCormick AL, Brown RH, Jr., Cudkowicz ME, et al. Quantification of reverse transcriptase in ALS and elimination of a novel retroviral candidate. Neurology 2008; 70(4): 278-83. DOI: 10.1212/01.wnl.0000297552.13219.b4

Klein JP, Sun Z, Staff NP. Association between ALS and retroviruses: evidence from bioinformatics analysis. BMC Bioinformatics 2019; 20(Suppl 24): 680. DOI: 10.1186/s12859-019-3249-8

Li W, Lee MH, Henderson L, et al. Human endogenous retrovirus-K contributes to motor neuron disease. Sci Transl Med 2015; 7(307): 307ra153. DOI: 10.1126/scitranslmed.aac8201

Gold J, Rowe DB, Kiernan MC, et al. Safety and tolerability of Triumeq in amyotrophic lateral sclerosis: the Lighthouse trial. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2019; 20(7-8): 595-604. DOI: 10.1080/21678421.2019.1632899

Bedlack R, The ALSUntangled Group. ALSUntangled.com 2009 [Available from: http://www.alsuntangled.com/completed.html].

The ALSUntangled Group. ALSUntangled 44: curcumin. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2018; 19(7-8): 623-629. DOI: 10.1080/21678421.2018.1440738

Small GW, Siddarth P, Li Z, et al. Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial. Am J Geriatr Psychiatry. DOI: 10.1016/j.jagp.2017.10.010

The ALSUntangled Group. ALSUntangled 53: Carnitine supplements. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2020: 1-7. DOI: 10.1080/21678421.2020.1726565

Harrison D, Mehta P, van Es MA, et al. "ALS reversals": demographics, disease characteristics, treatments, and co-morbidities. Amyotroph Lateral Scler Frontotemporal Degener 2018; 19(7-8): 495-499. DOI: 10.1080/21678421.2018.1457059

Peña-Quintana L, Llarena M, Reyes-Suárez D, Aldámiz-Echevarria L. Profile of sodium phenylbutyrate granules for the treatment of urea-cycle disorders: patient perspectives. Patient Prefer Adherence 2017; 11: 1489-1496. DOI: 10.2147/PPA.S136754

Kubota K, Niinuma Y, Kaneko M, et al. Suppressive effects of 4-phenylbutyrate on the aggregation of Pael receptors and endoplasmic reticulum stress. Journal of Neurochemistry 2006; 97(5): 1259-1268. DOI: 10.1111/j.1471-4159.2006.03782.x

Del Signore SJ, Amante DJ, Kim J, et al. Combined riluzole and sodium phenylbutyrate therapy in transgenic amyotrophic lateral sclerosis mice. Amyotrophic Lateral Sclerosis 2009; 10(2): 85-94. DOI: 10.1080/17482960802226148

Cudkowicz ME, Andres PL, Macdonald SA, et al. Phase 2 study of sodium phenylbutyrate in ALS. Amyotroph Lateral Scler 2009; 10(2): 99-106. DOI: 10.1080/17482960802320487

Daruich A, Picard E, Boatright JH, Behar-Cohen F. Review: The bile acids urso- and tauroursodeoxycholic acid as neuroprotective therapies in retinal disease. Mol Vis 2019; 25: 610-624.

Min JH, Hong YH, Sung JJ, et al. Oral solubilized ursodeoxycholic acid therapy in amyotrophic lateral sclerosis: a randomized cross-over trial. J Korean Med Sci 2012; 27(2): 200-6. DOI: 10.3346/jkms.2012.27.2.200

Elia AE, Lalli S, Monsurrò MR, et al. Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis. Eur J Neurol 2016; 23(1): 45-52. DOI: 10.1111/ene.12664

Paganoni S, Macklin EA, Hendrix S, et al. Trial of Sodium Phenylbutyrate–Taurursodiol for Amyotrophic Lateral Sclerosis. New England Journal of Medicine 2020; 383(10): 919-930. DOI: 10.1056/NEJMoa1916945

Chen P-C, Hsieh Y-C, Huang C-C, Hu C-J. Tamoxifen for amyotrophic lateral sclerosis: A randomized double-blind clinical trial. Medicine 2020; 99(22): e20423. DOI: 10.1097/MD.0000000000020423

Ngo ST, Steyn FJ, Huang L, et al. Altered expression of metabolic proteins and adipokines in patients with amyotrophic lateral sclerosis. Journal of the Neurological Sciences 2015; 357(1): 22-27. DOI: 10.1016/j.jns.2015.06.053

Mora JS, Genge A, Chio A, et al. Masitinib as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomized clinical trial. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2020; 21(1-2): 5-14. DOI: 10.1080/21678421.2019.1632346

Berry JD, Cudkowicz ME, Windebank AJ, et al. NurOwn, phase 2, randomized, clinical trial in patients with ALS. Safety, clinical, and biomarker results 2019; 93(24): e2294-e2305. DOI: 10.1212/WNL.0000000000008620

Thonhoff JR, Beers DR, Zhao W, et al. Expanded autologous regulatory T-lymphocyte infusions in ALS: A phase I, first-in-human study. Neurol Neuroimmunol Neuroinflamm 2018; 5(4): e465. DOI: 10.1212/NXI.0000000000000465

Rowe DB, Mathers S, Smith G, et al. Theme 9 Clinical trials and trial design. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2019; 20(sup1): 262-288. DOI: 10.1080/21678421.2019.1646997

Matharan M, Mathis S, Bonabaud S, et al. Minimizing the Diagnostic Delay in Amyotrophic Lateral Sclerosis: The Role of Nonneurologist Practitioners. Neurology Research International 2020; 2020: 1473981. DOI: 10.1155/2020/1473981

Bedlack R, Pogemiller A, Shefner J, et al. ALS clinical research learning institutes (ALS-CRLI): Empowering people with ALS to be research ambassadors. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2020; 21(3-4): 216-221. DOI: 10.1080/21678421.2019.1690519

Arthur KC, Calvo A, Price TR, et al. Projected increase in amyotrophic lateral sclerosis from 2015 to 2040. Nat Commun 2016; 7: 12408. DOI: 10.1038/ncomms12408

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Published

2021-02-19

How to Cite

Pridmore, W. (2021). Updates from the fray: rational off-label and over-the-counter prescribing in amyotrophic lateral sclerosis. RRNMF Neuromuscular Journal, 2(1). https://doi.org/10.17161/rrnmf.v2i1.14789

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Section

Looking Back and Looking Forward at Stuff (Reviews)