121:(ALS) in 2023. It was developed by Biogen under a licensing agreement with Ionis Pharmaceuticals. In trials the drug was found to lower levels of an ALS biomarker, neurofilament light change, and in long-term trial extensions to slow disease. Under the terms of the FDA's accelerated approval program, a confirmatory study will be conducted in presymptomatic gene carriers to provide additional evidence.
2156:
1325:
144:(FDA). Milasen "itself remains an investigational drug, and it is not suited for the treatment of other patients with Batten's disease" because it was customized for a single patient's specific mutation. However it is an example of
1103:
1913:
Elitt, Matthew S.; Barbar, Lilianne; Shick, H. Elizabeth; Powers, Berit E.; Maeno-Hikichi, Yuka; Madhavan, Mayur; Allan, Kevin C.; Nawash, Baraa S.; Gevorgyan, Artur S.; Hung, Stevephen; Nevin, Zachary S. (2020-07-01).
941:
Kim, Jinkuk; Hu, Chunguang; Moufawad El Achkar, Christelle; Black, Lauren E.; Douville, Julie; Larson, Austin; Pendergast, Mary K.; Goldkind, Sara F.; Lee, Eunjung A.; Kuniholm, Ashley; Soucy, Aubrie (2019-10-09).
1588:
Miller, Timothy; Cudkowicz, Merit; Shaw, Pamela J.; Andersen, Peter M.; Atassi, Nazem; Bucelli, Robert C.; Genge, Angela; Glass, Jonathan; Ladha, Shafeeq; Ludolph, Albert L.; Maragakis, Nicholas J. (2020-07-09).
2011:
Raymond, Gregory J.; Zhao, Hien Tran; Race, Brent; Raymond, Lynne D.; Williams, Katie; Swayze, Eric E.; Graffam, Samantha; Le, Jason; Caron, Tyler; Stathopoulos, Jacquelyn; O'Keefe, Rhonda (2019-08-22).
1075:
207:
1155:
1091:
2071:
Sztainberg, Yehezkel; Chen, Hong-mei; Swann, John W.; Hao, Shuang; Tang, Bin; Wu, Zhenyu; Tang, Jianrong; Wan, Ying-Wooi; Liu, Zhandong; Rigo, Frank; Zoghbi, Huda Y. (December 2015).
67:
that achieve wide tissue distribution with very long half-lives. For instance, many ASO-based drugs contain phosphorothioate substitutions and 2' sugar modifications to inhibit
1073:
U.S. Food and Drug
Administration, Silver Springs, Maryland. News Release: FDA grants accelerated approval to first drug for Duchenne muscular dystrophy, September 19, 2016.
1840:
Qian, Hao; Kang, Xinjiang; Hu, Jing; Zhang, Dongyang; Liang, Zhengyu; Meng, Fan; Zhang, Xuan; Xue, Yuanchao; Maimon, Roy; Dowdy, Steven F.; Devaraj, Neal K. (June 2020).
1310:
916:
1125:
1072:
332:
246:
677:
Weiss, B. (ed.): Antisense
Oligodeoxynucleotides and Antisense RNA : Novel Pharmacological and Therapeutic Agents, CRC Press, Boca Raton, FL, 1997.
1269:
841:"Drug delivery trends in clinical trials and translational medicine: challenges and opportunities in the delivery of nucleic acid-based therapeutics"
183:(ExonDys51) received FDA approval for the treatment of cases that can benefit from skipping exon 51 of the dystrophin transcript. In December 2019,
187:(Vyondys 53) received FDA approval for the treatment of cases that can benefit from skipping exon 53 of the dystrophin transcript. In August 2020,
238:
1504:
Bennett CF, Swayze EE (2010). "RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform".
804:
Bennett CF, Swayze EE (2010). "RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform".
50:
The common stem for antisense oligonucleotides drugs is -rsen. The substem -virsen designates antiviral antisense oligonucleotides.
1445:
1249:
191:(Viltepso) received FDA approval for the treatment of cases that can benefit from skipping exon 53 of the dystrophin transcript.
339:
enabling hepatocyte-specific delivery, greatly reducing dose requirements and side effect profile while increasing the level of
1718:
Hagemann, Tracy L.; Powers, Berit; Mazur, Curt; Kim, Aneeza; Wheeler, Steven; Hung, Gene; Swayze, Eric; Messing, Albee (2018).
458:
777:
1472:
1298:
2186:
1387:
Kristen, Arnt V; Ajroud-Driss, Senda; Conceição, Isabel; Gorevic, Peter; Kyriakides, Theodoros; Obici, Laura (2019-02-01).
1020:
689:
466:
430:
426:
98:. Newer formulations using conjugated ligands greatly enhances delivery efficiency and cell-type specific targeting.
2140:
Antisense Pharma: Promising Phase IIb
Results Of Targeted Therapy With AP 12009 In Recurrent Anaplastic Astrocytoma
540:
129:
Milasen is a novel individualized therapeutic agent that was designed and approved by the FDA for the treatment of
42:
site binding on pre-mRNA. Several ASOs have been approved in the United States, the
European Union, and elsewhere.
1229:
257:, and also approved for use in the US and EU in 2018 with orphan drug designation. Its mechanism-of-action is the
82:
Phosphorothioate ASOs can be delivered to cells without the need of a delivery vehicle. ASOs do not penetrate the
1206:
891:
619:
Morcos PA (June 2007). "Achieving targeted and quantifiable alteration of mRNA splicing with
Morpholino oligos".
378:
1775:
Meng, Linyan; Ward, Amanda J.; Chun, Seung; Bennett, C. Frank; Beaudet, Arthur L.; Rigo, Frank (February 2015).
682:
1987:
1638:
552:
512:
386:
359:
although this trial was discontinued on March 21, 2021, due to lack of efficacy. It is currently licensed to
223:
118:
1044:
136:
In 2019, a report was published detailing the development of milasen, an antisense oligonucleotide drug for
1304:
1212:
1131:
1097:
1092:"FDA grants accelerated approval to first targeted treatment for rare Duchenne muscular dystrophy mutation"
1050:
141:
418:
176:
2146:
95:
2176:
2073:"Reversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides"
1182:
917:"FDA approves treatment of amyotrophic lateral sclerosis associated with a mutation in the SOD1 gene"
584:
282:
203:
160:
1389:"Patisiran, an RNAi therapeutic for the treatment of hereditary transthyretin-mediated amyloidosis"
654:
462:
434:
356:
314:
As of 2020 more than 50 antisense oligonucleotides were in clinical trials, including over 25 in
278:
254:
335:
for hereditary transthyretin-mediated amyloidosis. In this formulation the ASO is conjugated to
30:(mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including
2181:
2139:
1720:"Antisense suppression of glial fibrillary acidic protein as a treatment for Alexander disease"
536:
470:
406:
398:
382:
331:
A follow-on drug to
Inotersen is being developed by Ionis Pharmaceuticals and under license to
1177:
446:
336:
290:
262:
145:
2084:
1927:
1853:
1788:
1517:
1388:
817:
589:
390:
315:
1045:"Drug Approval Package: Vitravene (Fomivirsen Sodium Intravitreal Injectable) NDA# 20-961"
8:
574:
438:
159:(marketed as Vitravene), was approved by the U.S. FDA in August 1998, as a treatment for
91:
83:
39:
2088:
1931:
1857:
1792:
764:. Methods in Molecular Biology. Vol. 764. Totowa, NJ: Humana Press. pp. 1–15.
759:
727:
702:
2113:
2072:
2048:
2013:
1969:
1956:
1915:
1895:
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1841:
1817:
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1700:
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1369:
1254:
976:
943:
865:
840:
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532:
2118:
2100:
2053:
2035:
1973:
1961:
1943:
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1804:
1757:
1739:
1704:
1692:
1684:
1620:
1612:
1570:
1521:
1480:
1446:"Updated: FDA approves drug that rescues babies with fatal neurodegenerative disease"
1418:
1410:
1373:
1361:
1021:"A Drug Was Made For Just One Child, Raising Hopes About Future Of Tailored Medicine"
981:
963:
870:
821:
783:
773:
732:
685:
678:
636:
516:
501:
478:
360:
1430:
1156:"Akcea and Ionis Announce Approval of Waylivra (volanesorsen) in the European Union"
2108:
2092:
2043:
2025:
1951:
1935:
1877:
1861:
1812:
1796:
1747:
1731:
1676:
1602:
1560:
1552:
1513:
1453:
1400:
1353:
1346:"FDA approves first-of-its kind targeted RNA-based therapy to treat a rare disease"
971:
955:
860:
852:
813:
765:
744:
722:
714:
628:
594:
528:
394:
258:
758:
Goodchild, John (2011). "Therapeutic
Oligonucleotides". In Goodchild, John (ed.).
2160:
1345:
1079:
474:
454:
414:
23:
1842:"Reversing a model of Parkinson's disease with in situ converted nigral neurons"
1357:
769:
2030:
1126:"FDA Approves Targeted Treatment for Rare Duchenne Muscular Dystrophy Mutation"
632:
569:
520:
489:
402:
140:, under an expanded-access investigational clinical protocol authorized by the
137:
130:
31:
1939:
1865:
1680:
1270:"FDA approves new orphan drug Kynamro to treat inherited cholesterol disorder"
222:(marketed as Kynamro) was approved by the FDA for the treatment of homozygous
2170:
2104:
2039:
1947:
1873:
1808:
1743:
1688:
1616:
1484:
1414:
1365:
1329:
967:
548:
544:
340:
266:
27:
1777:"Towards a therapy for Angelman syndrome by targeting a long non-coding RNA"
1664:
1639:"Roche drops Huntington's disease trial with once-promising drug tominersen"
1457:
63:
ASO-based drugs employ highly modified, single-stranded chains of synthetic
2122:
2057:
1965:
1891:
1826:
1761:
1696:
1624:
1574:
1525:
1422:
1000:
985:
874:
825:
787:
736:
703:"Antisense RNA technology for studying and modulating biological processes"
640:
450:
410:
371:
Clinical trials are ongoing for several diseases and conditions including:
199:
64:
1607:
1590:
1405:
1207:"Drug Approval Package: Kynamro (mipomersen sodium) Injection NDA #203568"
959:
718:
1916:"Suppression of proteolipid protein rescues Pelizaeus-Merzbacher disease"
442:
242:
188:
2096:
1800:
175:
oligos have been approved to treat specific groups of mutations causing
1988:"Research finds new approach to treating certain neurological diseases"
944:"Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease"
579:
509:
374:
286:
245:
219:
184:
180:
172:
156:
1735:
1556:
856:
564:
250:
234:
1591:"Phase 1–2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS"
500:
Several ASOs are currently being investigated in disease models for
2014:"Antisense oligonucleotides extend survival of prion-infected mice"
1386:
524:
422:
114:(marketed as Qalsody) was approved by the FDA for the treatment of
111:
87:
68:
326:
1328:
This article incorporates text from this source, which is in the
297:. In December 2016, nusinersen received regulatory approval from
265:, which allows it to interfere with and block the production of
229:
485:
294:
86:
when delivered systemically but they can distribute across the
133:. This therapy serves as an example of personalized medicine.
505:
482:
940:
269:. As such, it was the first FDA-approved siRNA therapeutic.
34:
mediated decay of the pre-mRNA, direct steric blockage, and
1587:
241:
in
October 2018. The application for inotersen was granted
115:
35:
16:
Form of treatment for genetic disorders and other illnesses
1541:"Silencing disease genes in the laboratory and the clinic"
301:
and soon after, from other regulatory agencies worldwide.
298:
53:
915:
Research, Center for Drug
Evaluation and (2023-04-25).
2070:
2010:
1912:
1717:
2144:
1665:"Antisense Oligonucleotides Targeting Lipoprotein(a)"
1663:
Langsted, Anne; Nordestgaard, Børge G. (2019-05-20).
194:
71:
degradation enabling vehicle-free delivery to cells.
1662:
1250:"F.D.A. Approves Genetic Drug to Treat Rare Disease"
1774:
1473:"Surprise Drug Approval Is Holiday Gift for Biogen"
621:
Biochemical and Biophysical Research Communications
1001:"Unique drug for a girl with deadly brain disease"
700:
277:In 2004, development of an antisense therapy for
2168:
1299:"Inotersen Orphan Drug Designation and Approval"
213:
106:
1839:
1293:
1291:
1158:(Press release). Akcea Therapeutics. 7 May 2019
1581:
1118:
694:
355:and RG6042) was tested in a phase 3 trial for
166:
1503:
1084:
838:
803:
327:Hereditary transthyretin-mediated amyloidosis
239:hereditary transthyretin-mediated amyloidosis
230:Hereditary transthyretin-mediated amyloidosis
1506:Annual Review of Pharmacology and Toxicology
1288:
832:
806:Annual Review of Pharmacology and Toxicology
799:
797:
701:Weiss B, Davidkova G, Zhou LW (March 1999).
304:
151:
751:
237:received FDA approval for the treatment of
22:is a form of treatment that uses antisense
1538:
495:
309:
272:
58:
2112:
2047:
2029:
1955:
1881:
1816:
1751:
1606:
1564:
1404:
998:
975:
864:
794:
757:
726:
914:
366:
1247:
391:autosomal dominant retinitis pigmentosa
346:
253:(sold under Onpattro) was developed by
2169:
1518:10.1146/annurev.pharmtox.010909.105654
1443:
936:
934:
932:
930:
818:10.1146/annurev.pharmtox.010909.105654
618:
1470:
1340:
1338:
1313:from the original on 19 December 2019
1106:from the original on 13 December 2019
101:
54:Pharmacokinetics and pharmacodynamics
1393:Neurodegenerative Disease Management
886:
884:
839:Xu L, Anchordoquy T (January 2011).
707:Cellular and Molecular Life Sciences
281:began. Over the following years, an
1539:Watts JK, Corey DR (January 2012).
1102:(Press release). 12 December 2019.
927:
459:Leber's hereditary optic neuropathy
351:Tominersen (also known as IONIS-HTT
321:
74:
13:
1335:
845:Journal of Pharmaceutical Sciences
208:familial chylomicronaemia syndrome
195:Familial chylomicronaemia syndrome
14:
2198:
2133:
881:
467:non-alcoholic fatty liver disease
431:familial chylomicronemia syndrome
427:epidermolysis bullosa dystrophica
293:under a licensing agreement with
124:
2154:
1323:
379:age related macular degeneration
2064:
2004:
1980:
1906:
1833:
1768:
1711:
1669:Current Atherosclerosis Reports
1656:
1631:
1595:New England Journal of Medicine
1532:
1497:
1464:
1437:
1380:
1262:
1241:
1199:
1170:
1148:
1136:(Press release). 12 August 2020
1066:
1037:
1013:
999:Gallagher, James (2019-10-12).
992:
948:New England Journal of Medicine
146:individualized genomic medicine
45:
908:
671:
647:
612:
1:
1444:Wadman M (23 December 2016).
1248:Pollack A (29 January 2013).
605:
553:spinocerebellar Ataxia Type 3
513:amyotrophic lateral sclerosis
387:amyotrophic lateral sclerosis
263:small interfering RNA (siRNA)
224:familial hypercholesterolemia
214:Familial hypercholesterolemia
119:amyotrophic lateral sclerosis
107:Amyotrophic lateral sclerosis
1305:Food and Drug Administration
1213:Food and Drug Administration
1132:Food and Drug Administration
1098:Food and Drug Administration
1051:Food and Drug Administration
761:Therapeutic Oligonucleotides
541:Pelizaeus–Merzbacher disease
148:therapeutical intervention.
142:Food and Drug Administration
7:
2187:Therapeutic gene modulation
1358:10.31525/fda2-ucm616518.htm
770:10.1007/978-1-61779-188-8_1
558:
419:Duchenne muscular dystrophy
206:(EMA) for the treatment of
177:Duchenne muscular dystrophy
167:Duchenne muscular dystrophy
38:content modulation through
10:
2203:
2031:10.1172/jci.insight.131175
1166:– via GlobeNewswire.
633:10.1016/j.bbrc.2007.04.172
363:by Ionis Pharmaceuticals.
96:intrathecal administration
1940:10.1038/s41586-020-2494-3
1866:10.1038/s41586-020-2388-4
1681:10.1007/s11883-019-0792-8
1183:European Medicines Agency
585:Oligonucleotide synthesis
305:Investigational therapies
283:antisense oligonucleotide
204:European Medicines Agency
161:cytomegalovirus retinitis
152:Cytomegalovirus retinitis
1545:The Journal of Pathology
316:advanced clinical trials
1458:10.1126/science.aal0476
1078:August 2, 2019, at the
496:Preclinical development
463:multiple system atrophy
435:frontotemporal dementia
343:reduction in patients.
310:Current clinical trials
279:spinal muscular atrophy
273:Spinal muscular atrophy
255:Alnylam Pharmaceuticals
59:Half-life and stability
1471:Grant C (2016-12-27).
407:centronuclear myopathy
399:cardiovascular disease
1608:10.1056/NEJMoa2003715
1406:10.2217/nmt-2018-0033
1350:Case Medical Research
960:10.1056/NEJMoa1813279
719:10.1007/s000180050296
655:"INN Bio Review 2022"
447:hereditary angioedema
367:Phase I and II trials
337:N-Acetylgalactosamine
291:Ionis Pharmaceuticals
179:. In September 2016,
590:Peptide nucleic acid
401:, elevated level of
357:Huntington's disease
347:Huntington's disease
202:was approved by the
2097:10.1038/nature16159
2089:2015Natur.528..123S
1932:2020Natur.585..397E
1858:2020Natur.582..550Q
1801:10.1038/nature13975
1793:2015Natur.518..409M
1724:Annals of Neurology
1477:Wall Street Journal
1187:. 24 September 2018
896:The ALS Association
575:Locked nucleic acid
537:Parkinson's disease
471:Parkinson's disease
383:Alzheimer's disease
318:(phase II or III).
92:cerebrospinal fluid
90:if injected in the
84:blood brain barrier
1255:The New York Times
533:myotonic dystrophy
333:Akcea Therapeutics
247:Akcea Therapeutics
102:Approved therapies
2083:(7580): 123–126.
1992:medicalxpress.com
1926:(7825): 397–403.
1852:(7813): 550–556.
1787:(7539): 409–412.
1736:10.1002/ana.25118
1557:10.1002/path.2993
1276:. 29 January 2013
954:(17): 1644–1652.
857:10.1002/jps.22243
779:978-1-61779-187-1
517:Angelman syndrome
502:Alexander disease
479:Stargardt disease
289:was developed by
26:(ASOs) to target
20:Antisense therapy
2194:
2177:Applied genetics
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2158:
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1309:. 24 July 2012.
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1234:
1230:"Summary Report"
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665:
651:
645:
644:
616:
595:RNA interference
529:multiple myeloma
483:STAT3-expressing
439:Fuchs' dystrophy
395:beta thalassemia
322:Phase III trials
259:active substance
218:In January 2013
116:SOD1- associated
24:oligonucleotides
2202:
2201:
2197:
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1178:"Waylivra EPAR"
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1080:Wayback Machine
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475:prostate cancer
455:IgA nephropathy
415:cystic fibrosis
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2134:External links
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2003:
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1601:(2): 109–119.
1580:
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1379:
1352:. 2018-08-10.
1334:
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1274:Fierce Biotech
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