&lt;p&gt;Inotersen: new promise for the treatment of hereditary transthyretin amyloidosis&lt;/p&gt;

Mathew, Veena; Wang, Annabel K.

doi:10.2147/dddt.s162913

Cited by 72 publications

(65 citation statements)

References 43 publications

(83 reference statements)

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“…This lead to the development of a new generation of ASOs: phosphorothioates (PS), locked nucleic acids (LNA), morpholinos, and peptide nucleic acids (PNA) based on either chemical modifications in phosphodiester linkage or in the ribose sugar moiety to overcome aforementioned challenges [ 61 ]. More recently, Inotersen (Tegsedi TM ), a second generation 2′-O-methoxyethyl modified ASO, received global approval for the treatment of hTTR in 2018 [ 62 ].…”

Section: Lipid-based Vectorsmentioning

confidence: 99%

Role of Lipid-Based and Polymer-Based Non-Viral Vectors in Nucleic Acid Delivery for Next-Generation Gene Therapy

et al. 2020

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The field of gene therapy has experienced an insurgence of attention for its widespread ability to regulate gene expression by targeting genomic DNA, messenger RNA, microRNA, and short-interfering RNA for treating malignant and non-malignant disorders. Numerous nucleic acid analogs have been developed to target coding or non-coding sequences of the human genome for gene regulation. However, broader clinical applications of nucleic acid analogs have been limited due to their poor cell or organ-specific delivery. To resolve these issues, non-viral vectors based on nanoparticles, liposomes, and polyplexes have been developed to date. This review is centered on non-viral vectors mainly comprising of cationic lipids and polymers for nucleic acid-based delivery for numerous gene therapy-based applications.

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Section: Lipid-based Vectorsmentioning

confidence: 99%

Role of Lipid-Based and Polymer-Based Non-Viral Vectors in Nucleic Acid Delivery for Next-Generation Gene Therapy

et al. 2020

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“…Tofersen (previously known as BIIB067) targets superoxide dismutase (SOD1) in ALS patients, reducing SOD1 concentrations in spinal fluid to preserve motor neurons and slow the progression of the disease. Inotersen is a 2′-MOE-modified ASO that reduces the production of TTR and improves disease course and quality of life in early hereditary TTR amyloidosis polyneuropathy (ATTR) ( Mathew and Wang, 2019 ).…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease

et al. 2020

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Alternative splicing of pre-mRNA contributes strongly to the diversity of cell- and tissue-specific protein expression patterns. Global transcriptome analyses have suggested that >90% of human multiexon genes are alternatively spliced. Alterations in the splicing process cause missplicing events that lead to genetic diseases and pathologies, including various neurological disorders, cancers, and muscular dystrophies. In recent decades, research has helped to elucidate the mechanisms regulating alternative splicing and, in some cases, to reveal how dysregulation of these mechanisms leads to disease. The resulting knowledge has enabled the design of novel therapeutic strategies for correction of splicing-derived pathologies. In this review, we focus primarily on therapeutic approaches targeting splicing, and we highlight nanotechnology-based gene delivery applications that address the challenges and barriers facing nucleic acid-based therapeutics.

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“…Inotersen, an antisense oligonucleotide, has been recently demonstrated to improve disease course and life quality in the early hereditary transthyretin amyloidosis polyneuropathy by reducing the production of transthyretin. 94 Inotersen has been clinically approved in the European Union for the management of adult patients with hATTR-PN on August 20, 2018. 95 And now it is accepted by USA, European Union, and Canada.…”

Section: Clinical Perspectivesmentioning

confidence: 99%

“…95 And now it is accepted by USA, European Union, and Canada. 94 Epigallocatechin-3-gallate (EGCG) (337, Figure 21) and resveratrol (338, Figure 21), two polyphenols isolated from green tea and grape skins, respectively, have been shown to stabilize TTR tetramers. 96,97 EGCG may inhibit the deposition of TTR pre-fiber by up to 50% and decompose amyloid.…”

Section: Clinical Perspectivesmentioning

confidence: 99%

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<p>Review on the Structures and Activities of Transthyretin Amyloidogenesis Inhibitors</p>

Guo¹,

Liu²,

Zheng³

et al. 2020

DDDT

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Transthyretin (TTR) is a tetrameric protein, and its dissociation, aggregation, deposition, and misfolding are linked to several human amyloid diseases. As the main transporter for thyroxine (T4) in plasma and cerebrospinal fluid, TTR contains two T4binding sites, which are docked with T4 and subsequently maintain the structural stability of TTR homotetramer. Affected by genetic disorders and detrimental environmental factors, TTR degrades to monomer and/or form amyloid fibrils. Reasonably, stabilization of TTR might be an efficient strategy for the treatment of TTR-related amyloidosis. However, only 10-25% of T4 in the plasma is bound to TTR under physiological conditions. Expectedly, T4 analogs with different structures aiming to bind to T4 pockets may displace the functions of T4. So far, a number of compounds including both natural and synthetic origin have been reported. In this paper, we summarized the potent inhibitors, including bisaryl structurebased compounds, flavonoids, crown ethers, and carboranes, for treating TTR-related amyloid diseases and the combination modes of some compounds binding to TTR protein.

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<p>Inotersen: new promise for the treatment of hereditary transthyretin amyloidosis</p>

Cited by 72 publications

References 43 publications

Role of Lipid-Based and Polymer-Based Non-Viral Vectors in Nucleic Acid Delivery for Next-Generation Gene Therapy

Role of Lipid-Based and Polymer-Based Non-Viral Vectors in Nucleic Acid Delivery for Next-Generation Gene Therapy

Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease

<p>Review on the Structures and Activities of Transthyretin Amyloidogenesis Inhibitors</p>

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