Targeting APOC3 in the familial chylomicronemia syndrome
Open accessAbstract
The familial chylomicronemia syndrome is a genetic disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis due to a deficiency in lipoprotein lipase (LPL). Currently, there are no effective therapies except for extreme restriction in the consumption of dietary fat. Apolipoprotein C-III (APOC3) is known to inhibit LPL, although there is also evidence that APOC3 increases the level of plasma triglycerides through an LPL-independent mechanism. We administered an inhibitor of APOC3 messenger RNA (mRNA), called ISIS 304801, to treat three patients with the familial chylomicronemia syndrome and triglyceride levels ranging from 1406 to 2083 mg per deciliter (15.9 to 23.5 mmol per liter). After 13 weeks of study-drug administration, plasma APOC3 levels were reduced by 71 to 90% and triglyceride levels by 56 to 86%. During the study, all patients had a triglyceride level of less than 500 mg per deciliter (5.7 mmol per liter) with treatment. These data support the role of APOC3 as a key regulator of LPL-independent pathways of triglyceride metabolism.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Plozasiran reduces hepatic APOC-III production by inhibiting mRNA transcription.
“Plozasiran, a siRNA-based therapeutic, reduces hepatic APOC-III production by inhibiting mRNA transcription [15].”
From The Efficacy and Safety of Plozasiran on Lipid Profile in Dyslipidemic Disorders: A Systematic Review and Meta-Analysis (2026) · cites this paper as [15]
The introductory passage identifies the studied drug as ISIS 304801, an antisense inhibitor—not plozasiran, a siRNA therapeutic. It says ISIS 304801 binds APOC3 mRNA and triggers its degradation by RNase H1, rather than inhibiting mRNA transcription. Our copy makes no claim about plozasiran itself. (LLM, conf=0.83)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredVolanesorsen is an antisense oligonucleotide that targets APOC3 mRNA and reduces plasma apolipoprotein C-III levels, chylomicronemia, and plasma triglyceride levels.
“Volanesorsen is an antisense oligonucleotide that targets APOC3 messenger RNA (mRNA) and reduces plasma apolipoprotein C-III levels, as well as the degree of chylomicronemia and plasma triglyceride levels.”
From Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome (2024) · cites this paper as [23]
The paper’s description of ISIS 304801 states that it binds APOC3 mRNA, and its Summary and ‘APOC3 Inhibition and Lipid Response’ sections report reductions in plasma APOC3, triglycerides, and measures of chylomicronemia. Our copy does not identify ISIS 304801 as volanesorsen, so it does not establish that the named drug is the one studied. (LLM, conf=0.82)
Experimental — accuracy not yet measuredApoCIII is a pleiotropic regulator of triglyceride-rich lipoprotein metabolism through LPL-dependent and LPL-independent pathways.
“We now understand apoCIII as a pleiotropic regulator of TGRL metabolism through LPL-dependent and LPLindependent pathways”
From The Forgotten Lipids: Triglycerides, Remnant Cholesterol, and Atherosclerotic Cardiovascular Disease Risk (2019) · cites this paper as [49]
Volanesorsen has been approved in the European Union and the United Kingdom for treatment of familial chylomicronemia syndrome and in Brazil for familial chylomicronemia syndrome and familial partial lipodystrophy.
“The agent has been approved in the European Union and the United Kingdom for the treatment of familial chylomicronemia syndrome and in Brazil for the treatment of familial chylomicronemia syndrome and familial partial lipodystrophy. 23-25”
From Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome (2024) · cites this paper as [23]
The Summary and Study Treatment sections describe a trial of ISIS 304801 in three patients, not regulatory approval. The paper mentions European approval of a different therapy, Glybera, but passages retrieved for approval, Brazil, and familial partial lipodystrophy do not address the claimed approvals of volanesorsen in the EU, UK, or Brazil. Page numbers are unavailable in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredOlezarsen appears to provide improved safety compared with volanesorsen while maintaining effective triglyceride reduction.
“Olezarsen appears to mitigate these risks while maintaining effective TG reduction [31][32][33]”
From Efficacy of Olezarsen in Severe Hypertriglyceridemia and Acute Pancreatitis Risk: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (2026) · cites this paper as [32]
The APOC3 Inhibition and Lipid Response section reports triglyceride reductions with ISIS 304801 in three patients, not with olezarsen. Searches for olezarsen, a safety comparison with volanesorsen, and adverse events found no passage in our copy addressing whether olezarsen mitigates those risks while retaining triglyceride-lowering efficacy. (LLM, conf=0.76)
Experimental — accuracy not yet measured
In three patients with FCS, volanesorsen reduced TG levels by up to 86% through a mechanism independent of LPL activity.
“In three patients with FCS, volanesorsen-reduced TG levels by up to 86%,72 through a mechanism independent of LPL activity.73”
From Clinical review on triglycerides (2020) · cites this paper as [72]
In a prior pilot study of three patients with familial chylomicronemia syndrome, antisense targeting of hepatic APOC3 mRNA with volanesorsen lowered apolipoprotein C-III and reduced triglycerides by 56 to 86%.
“in a recent pilot study in three patients with familial chylomicronemia syndrome, plasma apolipoprotein C-III levels were reduced by antisense targeting of hepatic APOC3 mRNA with volanesorsen, which led to reductions in triglyceride levels of 56 to 86%”
From Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome (2019) · cites this paper as [16]
Those pilot findings support the idea that apolipoprotein C-III also blocks an LPL-independent clearance pathway for triglyceride-rich lipoproteins.
“findings that support the hypothesis that apolipoprotein C-III also inhibits an LPL-independent pathway of triglyceride-rich lipoprotein clearance.16”
From Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome (2019) · cites this paper as [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
ESC/EAS Guidelines for the management of dyslipidaemias
Reiner, Ž., Catapano, A. L., De Backer, G., Graham, I., Taskinen, M.-R., Wiklund, O., Agewall, S., Alegria, E., Chapman, M. J., Durrington, P., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr158 · Cited by 3,549 · see citing works
Chapman, M. J., Ginsberg, H. N., Amarenco, P., Andreotti, F., Borén, J., Catapano, A. L., Descamps, O. S., Fisher, E., Kovanen, P. T., Kuivenhoven, J. A., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr112 · Cited by 1,227 · see citing works
Loss-of-Function Mutations in <i>APOC3,</i> Triglycerides, and Coronary Disease
The TG and HDL Working Group of the Exome Sequencing Project, N. H. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1307095 · Cited by 1,071 · see citing works
Loss-of-Function Mutations in <i>APOC3</i> and Risk of Ischemic Vascular Disease
Jørgensen, A. B., Frikke-Schmidt, R., Nordestgaard, B. G., & Tybjærg-Hansen, A. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1308027 · Cited by 919 · see citing works
Pollin, T. I., Damcott, C. M., Shen, H., Ott, S. H., Shelton, J., Horenstein, R. B., Post, W., McLenithan, J. C., Bielak, L. F., Peyser, P. A., et al. (2008) · Science · doi:10.1126/science.1161524 · Cited by 688 · see citing works
A specific apoprotein activator for lipoprotein lipase
LaRosa, J. C., Levy, R. I., Herbert, P. N., Lux, S. E., & Fredrickson, D. S. (1970) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(70)90468-7 · Cited by 668 · see citing works
Hypertriglyceridemia as a Result of Human apo <i>CII</i> Gene Expression in Transgenic Mice
Ito, Y., Azrolan, N., O'Connell, A., Walsh, A., & Breslow, J. L. (1990) · Science · doi:10.1126/science.2167514 · Cited by 539 · see citing works
Inhibition of lipoprotein lipase by an apoprotein of human very low density lipoprotein
Brown, W. V., & Baginsky, M. L. (1972) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(72)80149-9 · Cited by 493 · see citing works
Aalto‐Setälä, K., Fisher, E. A. A., Chen, X., Chajek‐Shaul, T., Hayek, T., Zechner, R., Walsh, A., Ramakrishnan, R., Ginsberg, H. N., & Breslow, J. L. (1992) · Journal of Clinical Investigation · doi:10.1172/jci116066 · Cited by 450 · see citing works
Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease
Petersen, K. F., Dufour, S., Hariri, A., Nelson-Williams, C., Foo, J. N., Zhang, X.-M., Dziura, J., Lifton, R. P., & Shulman, G. I. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0907295 · Cited by 428 · see citing works
Gaudet, D., Méthot, J., Déry, S., Brisson, D., Essiembre, C., Tremblay, G., Tremblay, K., de Wal, J., Twisk, J., van den Bulk, N., et al. (2013) · Gene Therapy · doi:10.1038/gt.2012.43 · Cited by 404 · see citing works
Self-citationGraham, M. J., Lee, R. G., Bell, T. A., Fu, W., Mullick, A. E., Alexander, V. J., Singleton, W., Viney, N., Geary, R., Su, J., et al. (2013) · Circulation Research · doi:10.1161/circresaha.111.300367 · Cited by 377 · see citing works
Self-citationMaeda, N., Li, H., Lee, D., Oliver, P. M., Quarfordt, S. H., & Osada, J. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31559-4 · Cited by 313 · see citing works
Apolipoprotein C-III: understanding an emerging cardiovascular risk factor
Ooi, E. M. M., Barrett, P. H. R., Chan, D. C., & Watts, G. F. (2008) · Clinical Science · doi:10.1042/cs20070308 · Cited by 282 · see citing works
Genetic determinants of plasma triglycerides
Johansen, C. T., Kathiresan, S., & Hegele, R. A. (2010) · Journal of Lipid Research · doi:10.1194/jlr.r009720 · Cited by 258 · see citing works
Mutations in LPL, APOC2, APOA5, GPIHBP1 and LMF1 in patients with severe hypertriglyceridaemia
Surendran, R. P., Visser, M. E., Heemelaar, S., Wang, J., Peter, J., Defesche, J. C., Kuivenhoven, J. A., Hosseini, M., Péterfy, M., Kastelein, J. J. P., et al. (2012) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2012.02516.x · Cited by 251 · see citing works
(2001) · Medical Entomology and Zoology · Cited by 227 · see citing works
Lipoprotein Genotype and Conserved Pathway for Exceptional Longevity in Humans
Atzmon, G., Rincon, M., Schechter, C. B., Shuldiner, A. R., Lipton, R. B., Bergman, A., & Barzilai, N. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040113 · Cited by 222 · see citing works
Apolipoprotein C-II and C-III levels in hyperlipoproteinemia
Schonfeld, G., George, P. K., Miller, J. P., Reilly, P., & Witztum, J. L. (1979) · Metabolism · doi:10.1016/0026-0495(79)90004-0 · Cited by 176 · see citing works
Self-citationKinnunen, P. K. J., & Ehnholm, C. (1976) · FEBS Letters · doi:10.1016/0014-5793(76)80145-7 · Cited by 166 · see citing works
Low-Density Lipoproteins Containing Apolipoprotein C-III and the Risk of Coronary Heart Disease
Mendivil, C. O., Rimm, E. B., Furtado, J., Chiuve, S. E., & Sacks, F. M. (2011) · Circulation · doi:10.1161/circulationaha.111.056986 · Cited by 136 · see citing works
Fredenrich, A., Giroux, L.-M., Tremblay, M., Krimbou, L., Davignon, J., & Cohn, J. S. (1997) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)37424-1 · Cited by 114 · see citing works
Doppler echocardiography for the diagnosis of acute cardiac allograft rejection
Desruennes, M., Corcos, T., Cabrol, A., et al. (1988) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(88)90357-9 · Cited by 108 · see citing works
Apolipoprotein C-III and hepatic triglyceride-rich lipoprotein production
Yao, Z., & Wang, Y. (2012) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328352dc70 · Cited by 100 · see citing works
Antisense Technology: An Emerging Platform for Cardiovascular Disease Therapeutics
Lee, R. G., Crosby, J. R., Baker, B. F., Graham, M. J., & Crooke, R. M. (2013) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-013-9495-7 · Cited by 66 · see citing works
Self-citationEtiology and risk of lactescent plasma and severe hypertriglyceridemia
Tremblay, K., Méthot, J., Brisson, D., & Gaudet, D. (2010) · Journal of clinical lipidology · doi:10.1016/j.jacl.2010.11.004 · Cited by 63 · see citing works
Self-citationUpdates on apolipoprotein CIII
Zheng, C. (2013) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000040 · Cited by 50 · see citing works
Brown, W. V., Brunzell, J. D., Eckel, R. H., & Stone, N. J. (2012) · Journal of clinical lipidology · doi:10.1016/j.jacl.2012.08.002 · Cited by 19 · see citing works
Alexander, V., Gaudet, D., Cheng, W., Flaim, J., Hughes, S. G., Singleton, W., & Geary, R. S. (2014) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(14)61453-4 · Cited by 11 · see citing works
Self-citationChristian, J., Bourgeois, N., & Lowe, K. (2011) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0b013e328349c4e5 · Cited by 8 · see citing works
Korpos, É., & Sorokin, L. M. (2013) · Diabetes · doi:10.2337/db13-0543 · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- [1]1. Brunzell JD, Deeb SS. Familial lipo- protein lipase deficiency, apo CII defi- ciency and hepatic lipase deficiency In: Scriver CR, Beaudet AI, Sly WS, Valle D, eds. The metabolic and molecular basis of inherited disease. 8th ed. New York: McGraw-Hill, 2000:2789-816.
- [3]3. Chait A, Brunzell JD. Chylomicronemia syndrome. Adv Intern Med 1992;37:249-73.
- [12]12. Ito Y, Azrolan N, O'Connell A, Walsh A, Breslow JL. Hypertriglyceridemia as a result of human apo CIII gene expres- sion in transgenic mice. Science 1990;249: 790-3.
Cited by
Sorted by citations
Ginsberg, H. N., Packard, C. J., Chapman, M. J., Borén, J., Aguilar-Salinas, C. A., Averna, M., Ference, B. A., Gaudet, D., Hegele, R. A., Kersten, S., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab551 · Cited by 979 · see citing works
Self-citationCrooke, S. T., Witztum, J. L., Bennett, C. F., & Baker, B. F. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.004 · Cited by 841 · see citing works
Self-citationSandesara, P. B., Virani, S. S., Fazio, S., & Shapiro, M. D. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00184 · Cited by 626 · see citing works
Cardiovascular and Metabolic Effects of <i>ANGPTL3</i> Antisense Oligonucleotides
Graham, M. J., Lee, R. G., Brandt, T. A., Tai, L.-J., Fu, W., Peralta, R., Yu, R., Hurh, E., Paz, E., McEvoy, B. W., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1701329 · Cited by 573 · see citing works
Self-citationClinical review on triglycerides
Laufs, U., Parhofer, K. G., Ginsberg, H. N., & Hegele, R. A. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz785 · Cited by 544 · see citing works
Antisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia
Gaudet, D., Alexander, V. J., Baker, B. F., Brisson, D., Tremblay, K., Singleton, W., Geary, R. S., Hughes, S. G., Viney, N. J., Graham, M. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1400283 · Cited by 528 · see citing works
Self-citationHong, D., Kurzrock, R., Kim, Y., Woessner, R., Younes, A., Nemunaitis, J., Fowler, N., Zhou, T., Schmidt, J., Jo, M., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aac5272 · Cited by 445 · see citing works
Self-citationChylomicronaemia–current diagnosis and future therapies
Brahm, A. J., & Hegele, R. A. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.26 · Cited by 356 · see citing works
Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity
Saleheen, D., Natarajan, P., Armean, I. M., Zhao, W., Rasheed, A., Khetarpal, S. A., Won, H.-H., Karczewski, K. J., O’Donnell-Luria, A. H., Samocha, K. E., et al. (2017) · Nature · doi:10.1038/nature22034 · Cited by 340 · see citing works
Metabolism of triglyceride-rich lipoproteins in health and dyslipidaemia
Borén, J., Taskinen, M.-R., Björnson, E., & Packard, C. J. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00676-y · Cited by 315 · see citing works
Targeting inflammation in metabolic syndrome
Welty, F. K., Alfaddagh, A., & Elajami, T. K. (2016) · Translational Research · doi:10.1016/j.trsl.2015.06.017 · Cited by 287 · see citing works
ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors
Gordts, P. L. S. M., Nock, R., Son, N.-H., Ramms, B., Lew, I., Gonzales, J. C., Thacker, B. E., Basu, D., Lee, R. G., Mullick, A. E., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86610 · Cited by 274 · see citing works
Self-citationOlezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome
Stroes, E. S. G., Alexander, V. J., Karwatowska-Prokopczuk, E., Hegele, R. A., Arca, M., Ballantyne, C. M., Soran, H., Prohaska, T. A., Xia, S., Ginsberg, H. N., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2400201 · Cited by 271 · see citing works
Self-citationMoulin, P., Dufour, R., Averna, M., Arca, M., Cefalù, A. B., Noto, D., D'Erasmo, L., Di Costanzo, A., Marçais, C., Alvarez-Sala Walther, L. A., et al. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.06.814 · Cited by 247 · see citing works
Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis
Zhu, C., Kim, K., Wang, X., Bartolome, A., Salomao, M., Dongiovanni, P., Meroni, M., Graham, M. J., Yates, K. P., Diehl, A. M., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aat0344 · Cited by 250 · see citing works
Self-citation2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia
Blumenthal, R. S., Morris, P. B., Gaudino, M., Johnson, H. M., Anderson, T. S., Bittner, V. A., Blankstein, R., Brewer, L. C., Cho, L., de Ferranti, S. D., et al. (2026) · JACC · doi:10.1016/j.jacc.2025.11.016 · Cited by 304 · see citing works
Wolska, A., Dunbar, R. L., Freeman, L. A., Ueda, M., Amar, M. J., Sviridov, D. O., & Remaley, A. T. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.10.025 · Cited by 231 · see citing works
Alexander, V. J., Xia, S., Hurh, E., Hughes, S. G., O’Dea, L., Geary, R. S., Witztum, J. L., & Tsimikas, S. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehz209 · Cited by 231 · see citing works
Self-citationGouni-Berthold, I., Alexander, V. J., Yang, Q., Hurh, E., Steinhagen-Thiessen, E., Moriarty, P. M., Hughes, S. G., Gaudet, D., Hegele, R. A., O'Dea, L. S. L., et al. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00046-2 · Cited by 232 · see citing works
Self-citationFrom Lipids to Inflammation: New Approaches to Reducing Atherosclerotic Risk
Shapiro, M. D., & Fazio, S. (2016) · Circulation Research · doi:10.1161/circresaha.115.306471 · Cited by 217 · see citing works
Tardif, J.-C., Karwatowska-Prokopczuk, E., Amour, E. S., Ballantyne, C. M., Shapiro, M. D., Moriarty, P. M., Baum, S. J., Hurh, E., Bartlett, V. J., Kingsbury, J., et al. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehab820 · Cited by 210 · see citing works
Self-citationXiao, C., Dash, S., Morgantini, C., Hegele, R. A., & Lewis, G. F. (2016) · Diabetes · doi:10.2337/db16-0046 · Cited by 212 · see citing works
Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia
Ballantyne, C. M., Vasas, S., Azizad, M., Clifton, P., Rosenson, R. S., Chang, T., Melquist, S., Zhou, R., Mushin, M., Leeper, N. J., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2404143 · Cited by 210 · see citing works
Self-citationOlezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk
Bergmark, B. A., Marston, N. A., Prohaska, T. A., Alexander, V. J., Zimerman, A., Moura, F. A., Murphy, S. A., Goodrich, E. L., Zhang, S., Gaudet, D., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2402309 · Cited by 198 · see citing works
Self-citationThe Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans
Borén, J., Packard, C. J., & Taskinen, M.-R. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00474 · Cited by 196 · see citing works
Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion
Wang, Y., Gusarova, V., Banfi, S., Gromada, J., Cohen, J. C., & Hobbs, H. H. (2015) · Journal of Lipid Research · doi:10.1194/jlr.m054882 · Cited by 189 · see citing works
Apolipoprotein C-III: from pathophysiology to pharmacology
Norata, G. D., Tsimikas, S., Pirillo, A., & Catapano, A. L. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.07.001 · Cited by 182 · see citing works
Lipid-Lowering Agents: Targets Beyond PCSK9
Hegele, R. A., & Tsimikas, S. (2019) · Circulation Research · doi:10.1161/circresaha.118.313171 · Cited by 171 · see citing works
Pechlaner, R., Tsimikas, S., Yin, X., Willeit, P., Baig, F., Santer, P., Oberhollenzer, F., Egger, G., Witztum, J. L., Alexander, V. J., et al. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.11.065 · Cited by 171 · see citing works
Self-citationPlozasiran (ARO-APOC3) for Severe Hypertriglyceridemia
Gaudet, D., Pall, D., Watts, G. F., Nicholls, S. J., Rosenson, R. S., Modesto, K., San Martin, J., Hellawell, J., & Ballantyne, C. M. (2024) · JAMA Cardiology · doi:10.1001/jamacardio.2024.0959 · Cited by 172 · see citing works
Self-citationDigenio, A., Dunbar, R. L., Alexander, V. J., Hompesch, M., Morrow, L., Lee, R. G., Graham, M. J., Hughes, S. G., Yu, R., Singleton, W., et al. (2016) · Diabetes Care · doi:10.2337/dc16-0126 · Cited by 170 · see citing works
Self-citationClinical and biochemical features of different molecular etiologies of familial chylomicronemia
Hegele, R. A., Berberich, A. J., Ban, M. R., Wang, J., Digenio, A., Alexander, V. J., D'Erasmo, L., Arca, M., Jones, A., Bruckert, E., et al. (2018) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2018.03.093 · Cited by 165 · see citing works
Self-citationChait, A., & Eckel, R. H. (2019) · Annals of Internal Medicine · doi:10.7326/m19-0203 · Cited by 128 · see citing works
Crooke, S. T., Baker, B. F., Witztum, J. L., Kwoh, T. J., Pham, N. C., Salgado, N., McEvoy, B. W., Cheng, W., Hughes, S. G., Bhanot, S., et al. (2017) · Nucleic Acid Therapeutics · doi:10.1089/nat.2016.0650 · Cited by 129 · see citing works
Self-citationWriting Committee Members, Blumenthal, R. S., Morris, P. B., Gaudino, M., Johnson, H. M., Anderson, T. S., Bittner, V. A., Blankstein, R., Brewer, L. C., Cho, L., et al. (2026) · Circulation · doi:10.1161/cir.0000000000001423 · Cited by 122 · see citing works
Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention
Michaeli, D. T., Michaeli, J. C., Albers, S., Boch, T., & Michaeli, T. (2023) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-023-00594-5 · Cited by 109 · see citing works
“After a first proof-of-concept study [173], volanesorsen’s dose-dependent efficacy has been established in a phase 1 trial of three patients with familial chylomicronemia syndrome (FCS) and elevated triglycerides [174].”
BackgroundYang, X., Lee, S.-R., Choi, Y.-S., Alexander, V. J., Digenio, A., Yang, Q., Miller, Y. I., Witztum, J. L., & Tsimikas, S. (2016) · Journal of Lipid Research · doi:10.1194/jlr.m066399 · Cited by 103 · see citing works
Self-citationEffects of <i>APOC3</i> Heterozygous Deficiency on Plasma Lipid and Lipoprotein Metabolism
Reyes-Soffer, G., Sztalryd, C., Horenstein, R. B., Holleran, S., Matveyenko, A., Thomas, T., Nandakumar, R., Ngai, C., Karmally, W., Ginsberg, H. N., et al. (2019) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.118.311476 · Cited by 97 · see citing works
Triglyceride-rich lipoproteins and remnants: targets for therapy?
Dallinga-Thie, G. M., Kroon, J., Borén, J., & Chapman, M. J. (2016) · Current Cardiology Reports · doi:10.1007/s11886-016-0745-6 · Cited by 90 · see citing works
Characterizing familial chylomicronemia syndrome: baseline data of the APPROACH study
Blom, D. J., O'Dea, L., Digenio, A., Alexander, V. J., Karwatowska-Prokopczuk, E., Williams, K. R., Hemphill, L., Muñiz-Grijalvo, O., Santos, R. D., Baum, S., et al. (2018) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2018.05.013 · Cited by 82 · see citing works
Self-citationStahel, P., Xiao, C., Hegele, R. A., & Lewis, G. F. (2018) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2017.12.007 · Cited by 75 · see citing works
An evolutionary trade-off between host immunity and metabolism drives fatty liver in male mice
Nikkanen, J., Leong, Y. A., Krause, W. C., Dermadi, D., Maschek, J. A., Van Ry, T., Cox, J. E., Weiss, E. J., Gokcumen, O., Chawla, A., et al. (2022) · Science · doi:10.1126/science.abn9886 · Cited by 77 · see citing works
Recent advances in triacylglycerol mobilization by the gut
Xiao, C., Stahel, P., Carreiro, A. L., Buhman, K. K., & Lewis, G. F. (2018) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2017.12.001 · Cited by 77 · see citing works
Borén, J., Watts, G. F., Adiels, M., Söderlund, S., Chan, D. C., Hakkarainen, A., Lundbom, J., Lundbom, N., Matikainen, N., Kahri, J., et al. (2015) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.115.305614 · Cited by 72 · see citing works
Hypertriglyceridemia—causes, significance, and approaches to therapy
Santos-Baez, L. S., & Ginsberg, H. N. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00616 · Cited by 66 · see citing works
ApoC-III ASO promotes tissue LPL activity in the absence of apoE-mediated TRL clearance
Ramms, B., Patel, S., Nora, C., Pessentheiner, A. R., Chang, M. W., Green, C. R., Golden, G. J., Secrest, P., Krauss, R. M., Metallo, C. M., et al. (2019) · Journal of Lipid Research · doi:10.1194/jlr.m093740 · Cited by 59 · see citing works
Self-citationRole of apolipoprotein C-III overproduction in diabetic dyslipidaemia
Adiels, M., Taskinen, M., Björnson, E., Andersson, L., Matikainen, N., Söderlund, S., Kahri, J., Hakkarainen, A., Lundbom, N., Sihlbom, C., et al. (2019) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13744 · Cited by 55 · see citing works
Rocha, N. A., East, C., Zhang, J., & McCullough, P. A. (2017) · Current Atherosclerosis Reports · doi:10.1007/s11883-017-0697-3 · Cited by 54 · see citing works
Arca, M., Hsieh, A., Soran, H., Rosenblit, P., O’Dea, L., & Stevenson, M. (2018) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2018.1487290 · Cited by 49 · see citing works
Injection site reactions after subcutaneous oligonucleotide therapy
van Meer, L., Moerland, M., Gallagher, J., van Doorn, M. B. A., Prens, E. P., Cohen, A. F., Rissmann, R., & Burggraaf, J. (2016) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12961 · Cited by 45 · see citing works
Novel therapeutics in hypertriglyceridemia
Gryn, S. E., & Hegele, R. A. (2015) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000231 · Cited by 44 · see citing works
Helkkula, P., Kiiskinen, T., Havulinna, A. S., Karjalainen, J., Koskinen, S., Salomaa, V., Daly, M. J., Palotie, A., Surakka, I., Ripatti, S., et al. (2021) · PLOS Genetics · doi:10.1371/journal.pgen.1009501 · Cited by 47 · see citing works
Volanesorsen: A New Era in the Treatment of Severe Hypertriglyceridemia
Kolovou, G., Kolovou, V., & Katsiki, N. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11040982 · Cited by 33 · see citing works
Therapeutic targets of triglyceride metabolism as informed by human genetics
Bauer, R. C., Khetarpal, S. A., Hand, N. J., & Rader, D. J. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.02.005 · Cited by 32 · see citing works
Hegele, R. A. (2016) · Journal of Lipid Research · doi:10.1194/jlr.c070946 · Cited by 31 · see citing works
Building a better understanding of the burden of disease in familial chylomicronemia syndrome
Ahmad, Z., Halter, R., & Stevenson, M. (2017) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2017.1251839 · Cited by 28 · see citing works
Tramontano, D., D'Erasmo, L., Larouche, M., Brisson, D., Lauzière, A., Di Costanzo, A., Bini, S., Minicocci, I., Covino, S., Baratta, F., et al. (2025) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2025.119146 · Cited by 23 · see citing works
Self-citationRoundtable discussion: Familial chylomicronemia syndrome: Diagnosis and management
Brown, W. V., Goldberg, I., Duell, B., & Gaudet, D. (2018) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2018.02.018 · Cited by 21 · see citing works
Self-citationMahmoud, A., Abdelsayed, K., Mohamed, A. A., Najah, Q., Abdulkader, A., Ali, K., Tabassum, S., Abouzid, M. R., Abdelazeem, B., & Mills, J. D. (2025) · Lipids in Health and Disease · doi:10.1186/s12944-024-02389-2 · Cited by 17 · see citing works
Targeting RNA to lower triglycerides: long strides from short molecules
Qamar, A., Libby, P., & Bhatt, D. L. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehz321 · Cited by 14 · see citing works
Sydhom, P., Al-Quraishi, B., Gohar, A., El-Shawaf, M., Shehata, N., Ataya, M., Sydhom, M., Awwad, N., Motawade, H., Naji, N., et al. (2026) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-025-07798-8 · Cited by 5 · see citing works
“Plozasiran, a siRNA-based therapeutic, reduces hepatic APOC-III production by inhibiting mRNA transcription [15].”
A novel mouse model of familial combined hyperlipidemia and atherosclerosis
Chen, M.-J., Xu, Y.-T., Sun, L., Wang, Z.-H., Little, P. J., Wang, L., Xian, X.-D., Weng, J.-P., & Xu, S.-W. (2024) · Acta Pharmacologica Sinica · doi:10.1038/s41401-024-01241-8 · Cited by 5 · see citing works
Rehman, A., Rajdeep, D., Mohnkern, J. D., & Lin, J. (2026) · Digestive Diseases and Sciences · doi:10.1007/s10620-026-09846-1 · Cited by 2 · see citing works
“Olezarsen appears to mitigate these risks while maintaining effective TG reduction [32–34].”
- Authors
- Gaudet, D., Brisson, D., Tremblay, K., Alexander, V. J., Singleton, W., Hughes, S. G., Geary, R. S., Baker, B. F., Graham, M. J., Crooke, R. M., & Witztum, J. L.
- Affiliations
- University of California San Diego (US)
- Université de Montréal (CA)
- Ionis Pharmaceuticals (United States) (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2014-12-04
- Volume
- 371
- Issue
- 23
- Pages
- 2200-2206
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2032456325
- Cited by
- 491
- References
- 31
- Citations by year
- 2026: 32 · 2025: 39 · 2024: 32 · 2023: 35 · 2022: 33 · 2021: 38 · 2020: 54 · 2019: 39 · 2018: 48 · 2017: 47 · 2016: 55 · 2015: 36 · 2014: 2
- FWCI
- 31.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
- Keywords
- familial chylomicronemia syndrome, apolipoprotein C-III, lipoprotein lipase, hypertriglyceridemia, recurrent pancreatitis, triglyceride metabolism, plasma triglycerides
- MeSH terms
- Humans, Lipoprotein Lipase, Hyperlipoproteinemia Type I, Mutation, Oligonucleotides, RNA, Messenger, Triglycerides, Apolipoprotein C-III
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
