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Overview

Basic Info

Drug Type

ASO

Synonyms

ENA oligonucleotides, duchenne muscular dystrophy therapeutics - Daiichi Sankyo/Orphan Disease Treatment Institute

+ [1]

Target

dystrophin

Mechanism

DMD gene modulators

Therapeutic Areas

Nervous System DiseasesCongenital DisordersSkin and Musculoskeletal Diseases+ [1]

Active Indication

Muscular Dystrophy, Duchenne

Inactive Indication-

Originator Organization

Daiichi Sankyo Co., Ltd.

Active Organization

Daiichi Sankyo Co., Ltd.

Inactive Organization

Orphan Disease Treatment Institute Co., Ltd.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

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Gene Sequence

Sequence Code 32858997

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Antinuclear antibody (ANA) detection by indirect immunofluorescence (IIF) is instrumental in the evaluation of systemic autoimmune diseases (SADs). The dense fine speckled (DFS) ANA staining predominantly associates with anti-DFS70, an autoantibody that is thought to exclude the presence of SAD. However, the DFS pattern may mask the presence of other ANA patterns that may be clinically relevant. Our laboratory uses the HEp2010 substrate which contains both HEp2 and liver substates. The aim of this study was to determine whether negative liver nucleus immunofluorescence could exclude the presence of antibodies to extractable nuclear antigens (ENA) in sera with DFS-like patterns. One hundred consecutive sera samples suspicious for DFS pattern, along with 15 sera of control patterns (positive metaphase bars) were included in the study. Each sample was examined separately on HEp2010 (Euroimmun) and liver by two independent readers. Anti-DFS70 was assessed by line and chemiluminescent immunoassays. DFS-like sera were more likely to be liver nucleus-negative compared with control sera. Of the liver-negative sera, 61/64 (95.3%) were deemed anti-ENA negative. Using the liver substrate in the evaluation of anti-ENA had a sensitivity of 90.0% and a negative predictive value of 95.4%. In our cohort, concurrent evaluation of sera with the liver substrate helped rule out the presence of other anti-ENA. This technique may be a safeguard for DFS-like ANA patterns that may mask underlying anti-ENA on IIF.

01 Nov 2024·Toxicology

Unexpected antagonism of deoxynivalenol and enniatins in intestinal toxicity through the Ras/PI3K/AKT signaling pathway

Article

Author: Sun, Xiulan ; Tang, Lili ; Tang, Luyao ; Wang, Jia-Sheng ; Sheng, Lina ; Ye, Yongli ; Ning, Xiao ; Sun, Jiadi

Deoxynivalenol (DON) is a kind of widespread traditional Fusarium mycotoxins in the environment, and its intestinal toxicity has received considerable attention. Recently, the emerging Fusarium mycotoxin enniatins (ENNs) have also been shown to frequently coexist with DON in animal feed and food with large consumption. However, the mechanism of intestinal damage caused by the two mycotoxins co-exposure remains unclear. In this study, Caco-2 cell line was used to investigate the combined toxicity and potential mechanisms of four representative ENNs (ENA, ENA₁, ENB, and ENB₁) and DON. The results showed that almost all mixed groups showed antagonistic effects, particularly ENB at 1/4 IC₅₀ (CI = 6.488). Co-incubation of ENNs mitigated the levels of signaling molecule levels disrupted by DON, including reactive oxygen species (ROS), calcium mobilization (Ca²⁺), adenosine triphosphate (ATP). The differentially expressed genes (DEGs) between the mixed and ENB groups were significantly enriched in the Ras/PI3K/Akt signaling pathway, including 28 up-regulated genes and 40 down-regulated genes. Quantitative real-time PCR further confirmed the lower expression of apoptotic gene in the mixed group, thereby reducing the cytotoxic effects caused by DON exposure. This study emphasizes that co-exposure of ENNs and DON reduces cytotoxicity by regulating the Ras/PI3K/Akt signaling pathway. Our results provide the first comprehensive evidence about the antagonistic toxicity of ENNs and DON on Caco-2 cells, and new insights into mechanisms investigated by transcriptomics.

01 Oct 2024·Dental Materials

Do all ceramic and composite CAD-CAM materials exhibit equal bonding properties to implant Ti-base materials? An Interfacial Fracture Toughness Study

Article

Author: Eldafrawy, Maher ; Sanchez, Christelle ; Herman, Raphael ; Karevan, Yousef ; Sadoun, Michaël ; Mainjot, Amélie

OBJECTIVESTo compare the interfacial fracture toughness (IFT) with or without aging, of four different classes of CAD-CAM ceramic and composite materials bonded with self-adhesive resin cement to titanium alloy characteristic of implant abutments.METHODSHigh translucent zirconia (Katana; KAT), lithium disilicate-based glass-ceramic (IPS. emax.CAD; EMX), polymer-infiltrated ceramic network material (PICN) (Vita Enamic; ENA), and dispersed filler composite (Cerasmart 270; CER) were cut into equilateral triangular prisms and bonded to titanium prisms with identical dimensions using Panavia SA Cement Universal. The surfaces were pretreated following the manufacturers' recommendations and developed interfacial area ratio (Sdr) of the pretreated surfaces was measured. IFT was determined using the Notchless Triangular Prism test in a water bath at 36 °C before and after thermocycling (10,000 cycles) (n = 40 samples/material).RESULTSIFT of the materials ranged from 0.80 ± 0.25 to 1.10 ± 0.21 MPa.m^1/2 before thermocycling and from 0.71 ± 0.24 to 1.02 ± 0.25 MPa.m^1/2 after thermocycling. There was a statistical difference between IFT of CER and the two top performers in each scenario: KAT and EMX before aging, and KAT and ENA after aging. Thermocycling significantly decreased IFT of EMX. The Weibull modulus of IFT was similar for all materials and remained so after thermocycling. Sdr measurements revealed that ENA (7.60)>Ti (4.97)>CER (2.85)>KAT (1.09)=EMX (0.96).SIGNIFICANCEDispersed filler CAD-CAM composite showed lower performance than the other materials. Aging only affected IFT of Li-Si glass-ceramic, whereas zirconia and PICN performed equally well, probably due to their chemical bonding potential and surface roughness respectively.

100 Deals associated with Renadirsen

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Muscular Dystrophy, Duchenne	Preclinical	JP	Orphan Disease Treatment Institute Co., Ltd.	01 Oct 2015
Muscular Dystrophies	Discovery	JP	Orphan Disease Treatment Institute Co., Ltd.	28 Jan 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02667483 (CTgov)	Phase 1/2	Muscular Dystrophy, Duchenne	8	DS-5141b (All: DS-5141b 2.0 mg/kg)	syxpuecvtc(pgmblxeijz) = fzsguinexl jfxmlbjism (rpjwpxvolv, kzhesiirjv - lnmozronyi) View more	-	07 Mar 2024
				DS-5141b (All: DS-5141b 6.0 mg/kg)	syxpuecvtc(pgmblxeijz) = ctomccseou jfxmlbjism (rpjwpxvolv, gyukstahdd - miqolkhcop) View more
ASH2023	Phase 1/2	-	51	ASTX727 + VEN + IVO	(dvivrnjepx) = pfbkewzfvv lnfzetbvmv (wnkzbmrkkr ) View more	-	11 Dec 2023
				ASTX727 + VEN + ENA	(dvivrnjepx) = nhmzlecejv lnfzetbvmv (wnkzbmrkkr ) View more
AG221-AML-005 (EHA2021)	Not Applicable	IDH2 mutation Acute Myeloblastic Leukemia	101	ENA+AZA	fubnznfizu(ufztqwjzzj) = fzeothedba qkbsnpsqzm (yptbovdmux ) View more	-	09 Jun 2021
				AZA only	fubnznfizu(ufztqwjzzj) = vzyvvujxbp qkbsnpsqzm (yptbovdmux ) View more