Figures & data
Figure 1 Protein synthesis.
Notes: (A) Watson–Crick complement base pairing and triplet codons. (B) From DNA to protein. Reproduced from Antisense oligonucleotides and other genetic therapies made simple, Rossor AM, Reilly MM, Sleigh JN. Pract Neurol. 18(2):126–131. copyright 2018 with permission from BMJ Publishing Group Ltd.Citation34
Figure 2 Mechanisms of oligonucleotides.
Notes: (A) ASOs use RNase H-mediated mRNA degradation, steric blocking, or splicing modulation. (B) RNAi–siRNA (dsRNA) is cleaved by Dicer and triggers RISC cleavage of mRNA. Reproduced from Antisense oligonucleotides and other genetic therapies made simple, Rossor AM, Reilly MM, Sleigh JN. Pract Neurol. 18(2):126–131. copyright 2018 with permission from BMJ Publishing Group Ltd.Citation34
Abbreviations: ASO, antisense oligonucleotide; RISC, RNA-induced silencing complexes.
Abbreviations: ASO, antisense oligonucleotide; RISC, RNA-induced silencing complexes.
Figure 3 Pharmacodynamic effects of IONIS-TTRRX in healthy volunteers.
Notes: Suppressing transthyretin production in mice, monkeys and humans using 2nd-generation antisense oligonucleotides, Ackermann EJ, Guo S, Benson MD, et al, Amyloid. 2016;23(3):148–157 reprinted by permission of the publisher (Taylor & Francis Ltd, http://www.tandfonline.com).Citation40 (A) Change in Plasma TTR levels in 50, 100, 200, 300, and 400 mg treatment groups. (B) Change in Plasma RBP4 levels in 50, 100, 200, 300, and 400 mg treatment groups.
Abbreviation: chg, change.
Abbreviation: chg, change.
Figure 4 Primary end points: Inotersen Phase III study.
Notes: From the New England Journal of Medicine, Benson MD, Waddington-Cruz M, Berk JL, et al. Inotersen treatment for patients with hereditary transthyretin amyloidosis. N Engl J Med. 2018;379(1):22–31. Copyright © 2018 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.Citation33 (A) Change from baseline between Inotersen and placebo groups for mNIS+7. (B) Change from baseline between Inotersen and placebo groups for QOL-DN questionnaire.
Abbreviations: mNIS +7, modified Neuropathy Impairment Score +7; QOL-DN, Quality of Life Questionnaire-Diabetic Neuropathy.
Abbreviations: mNIS +7, modified Neuropathy Impairment Score +7; QOL-DN, Quality of Life Questionnaire-Diabetic Neuropathy.
Figure 5 Inotersen timeline.
Note: Reprinted by permission from Springer Nature: Springer Nature, Drugs, Inotersen: first global approval, Keam SJ, 2018;78(13):1371–1376.Citation42
Abbreviations: ATTR, TTR amyloidosis; US FDA, US Food and Drug Administration; MAA, marketing authorization application; NDA, new drug application.
Abbreviations: ATTR, TTR amyloidosis; US FDA, US Food and Drug Administration; MAA, marketing authorization application; NDA, new drug application.
