A Phase 1/2, First in Human, Multiple-dose, 2-part Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NS-050/NCNP-03 in Boys With Duchenne Muscular Dystrophy (DMD)

This is a Phase 1/2 study of Multiple-Ascending Dose (MAD) levels for 12 weeks of treatment followed by 24 weeks of open-label treatment with a selected dose of NS-050/NCNP-03 administered once weekly to ambulant boys with DMD, who have a DMD mutation amenable to exon 50 skipping.

开始日期2024-07-01

申办/合作机构

NS Pharma, Inc.

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100 项与 NS-050 相关的临床结果

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100 项与 NS-050 相关的转化医学

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100 项与 NS-050 相关的专利（医药）

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项与 NS-050 相关的文献（医药）

2019-01-01·Ayu

An experimental study to evaluate the effect of Nitya Sevaniya (daily consumable) and Nitya Asevaniya (daily non-consumable) food items on albino rats

Article

作者: Nariya, Mukesh Kumar B ; Vyas, Mahesh ; Deshmukh, Saylee

BACKGROUND:

As per Ayurveda, Nitya Sevaniya (NS) food items are recommended for daily intake while Nitya Asevaniya (NAS) food items should be avoided for daily intake due to their systemic wholesome and unwholesome effects after consumption, respectively.

AIM AND OBJECTIVES:

The present study was conducted to perform in vivo safety evaluation of selected Nitya Sevaniya and Nitya Asevaniya food items.

MATERIALS AND METHODS:

Thirty rats were randomly divided into five groups-each containing six Charle's Foster strain albino rats. Group 1 served as standard diet group, groups 2 and 3 served as test drug received groups namely NS50 and NS100, in which 50% and 100% mixture of Nitya Sevaniya food was administered, respectively. Group 4 and 5 as test drug received groups Nitya Asevaniya 50 (NAS50) and Nitya Asevaniya 100 (NAS100), in which 50% and 100% Nitya Asevaniya food mixtures was administered, respectively. The test diet was administered orally in the form of freshly prepared pellet twice a day ad libitum for 90 days. Parameters studied were gross behavior, body and organ weight, food and water intake, fecal and urine output, hematological and biochemical parameters, electrocardiogram and histology of various organs.

RESULTS:

In the NAS100 group, a significant change was observed in 20 of 47 parameters in view of pathological aspect. Among them, three parameters, i.e., platelet count, serum glutamic-oxaloacetic transaminase (SGOT) and indirect bilirubin were above normal limits, while other parameters were within the normal limits. No significant change was observed in any of the parameters in the NS50 and NS100 group after 90 days of administration as compared with the control group.

CONCLUSION:

Considering findings of this study, it is concluded that selected NS food items are safe while consumption of only selected Nitya Asevaniya food items (when administered in 100% dose) for 90 days have the potential of inflammatory changes in the liver, spleen; fat deposition in kidney and impairment of cardiac and renal functions.

2011-12-01·Infection and immunity2区 · 医学

Ehrlichia chaffeensis Induces Monocyte Inflammatory Responses through MyD88, ERK, and NF-κB but Not through TRIF, Interleukin-1 Receptor 1 (IL-1R1)/IL-18R1, or Toll-Like Receptors

2区 · 医学

Article

作者: Junji Matsuo ; Yumi Kumagai ; Xin Li ; Koshiro Miura ; M. Akhlakur Rahman ; Yasuko Rikihisa

ABSTRACT:

Human monocytic ehrlichiosis, an influenza-like illness accompanied by signs of hepatitis, is caused by infection of monocytes/macrophages with a lipopolysaccharide-deficient bacterium,Ehrlichia chaffeensis. TheE. chaffeensisstrain Wakulla induces diffuse hepatitis with neutrophil infiltration in mice with severe combined immunodeficiency, which is accompanied by strong CXCL2 (mouse functional homolog of interleukin-8 [IL-8]) and tumor necrosis factor alpha (TNF-α) expression in the liver. In this study, we found that expression of IL-1β, CXCL2, and TNF-α was induced by strain Wakulla in mouse bone marrow-derived macrophages; this expression was dependent on MyD88, but not on TRIF, TLR2/4, IL-1R1/IL-18R1, or endosome acidification. When the human leukemia cell line THP-1 was exposed toE. chaffeensis, significant upregulation of IL-8, IL-1β, and TNF-α mRNA and extracellular regulated kinase 2 (ERK2) activation were detected. U0126 (inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 [MEK1/2] upstream of ERK), manumycin A (Ras inhibitor), BAY43-9006 (Raf-1 inhibitor), and NS-50 (inhibitor of NF-κB nuclear translocation) inhibited the cytokine gene expression. A luciferase reporter assay using HEK293 cells, which lack Toll-like receptors (TLRs), showed activation of both the IL-8 promoter and NF-κB byE. chaffeensis. Activation of the IL-8 promoter in transfected HEK293 cells was inhibited by manumycin A, BAY43-9006, U0126, and transfection with a dominant-negative Ras mutant. These results indicate that theE. chaffeensisWakulla strain can induce inflammatory responses through MyD88-dependent NF-κB and ERK pathways, without the involvement of TRIF and TLRs.

2007-02-01·International journal of pharmaceutics2区 · 医学

Fetuin mediates hepatic uptake of negatively charged nanoparticles via scavenger receptor

2区 · 医学

Article

作者: Susumu Nagayama ; Yoshiko Fukuoka ; Kazutaka Higaki ; Mitsuru Hashida ; Toshikiro Kimura ; Yoshinobu Takakura ; Ken ichi Ogawara ; Keiko Minato

We tried to evaluate the possible involvement of fetuin in the scavenger receptors (SRs)-mediated hepatic uptake of polystyrene nanospheres with the size of 50 nm (NS-50), which has surface negative charge (zeta potential=-21.8+/-2.3 mV). The liver perfusion studies in rats revealed that the hepatic uptake of NS-50 pre-coated with fetuin (NS-50-fetuin) was significantly inhibited by poly inosinic acid (poly I), a typical inhibitor of SRs, whereas that of plain NS-50 or NS-50 pre-coated with BSA (NS-50-BSA) was not. The uptake of NS-50-fetuin by cultured Kupffer cells was also significantly inhibited by poly I, and anti-class A scavenger receptors (SR-A) antibody, suggesting that fetuin on NS-50 mediated the recognition and internalization of NS-50 by Kupffer cells and at least SR-A would be responsible for the uptake. Taken that Western blot analysis confirmed that fetuin certainly adsorbed on the surface of NS-50 after the incubation of NS-50 with serum, the results obtained in the present study indicate that fetuin would be one of the serum proteins that were substantially involved in the hepatic uptake of NS-50 via SRs.

项与 NS-050 相关的新闻（医药）

2024-09-10

·PRNewswire

FDA Grants Rare Pediatric Disease Designation to NS-050/NCNP-03 for the Treatment of Duchenne Muscular Dystrophy

PARAMUS, N.J., Sept. 10, 2024 /PRNewswire/ -- NS Pharma, Inc. (NS Pharma), a subsidiary of Nippon Shinyaku Co., Ltd. (Nippon Shinyaku), announced that the Food and Drug Administration (FDA) has granted rare pediatric disease designation to NS-050/NCNP-03 which is being developed for the treatment of Duchenne muscular dystrophy (Duchenne). The FDA's rare pediatric disease designation is granted for treatments of serious or life-threatening diseases that affect children under the age of 18 and fewer than 200,000 patients in the United States. Continue Reading We are grateful for this designation which can help us accelerate the development of this therapy for Duchenne. Post this Yukiteru Sugiyama, PhD, NS Pharma President "The journey from first symptom to diagnosis and finally treatment can be long and challenging for patients with rare diseases and their caregivers," said NS Pharma President Yukiteru Sugiyama, Ph.D. "We are grateful for this designation which can help us accelerate the development of this therapy for Duchenne." Duchenne is a progressive muscle wasting disease caused by a deficiency of the dystrophin protein. It leads to weakness of skeletal, cardiac and pulmonary muscles. There are many types of genetic mutations that can cause Duchenne, and NS-050/NCNP-03 is being developed to treat patients with confirmed gene mutations amenable to exon 50 skipping therapy. NS-050/NCNP-03 is an antisense oligonucleotide co-discovered by the National Center of Neurology and Psychiatry (NCNP) and Nippon Shinyaku. NS-050/NCNP-03 skips part of the genetic information of the dystrophin gene and produces a functional dystrophin protein with a slightly shorter chain length, which is expected to have the effect of suppressing muscle function deterioration. NS Pharma is working to develop products for patients with rare diseases. We are preparing a Phase 1 / 2 study to evaluate the safety and efficacy of NS-050/NCNP-03 in patients with Duchenne in Japan and the United States. About Duchenne Muscular Dystrophy (Duchenne) Duchenne is a progressive form of muscular dystrophy that occurs primarily in males. It causes progressive weakness and loss of skeletal, cardiac, and respiratory muscles. Early signs of Duchenne may include delayed ability to sit, stand or walk. There is a progressive loss of mobility, and by adolescence, patients with Duchenne may require the use of a wheelchair. Cardiac and respiratory muscle problems begin in the teenage years and lead to serious, life-threatening complications. For more information about Duchenne, please visit wespeakduchenne.com. About NS Pharma, Inc. NS Pharma, Inc., is a wholly owned subsidiary of Nippon Shinyaku Co., Ltd. NS Pharma is a registered trademark of the Nippon Shinyaku Co., Ltd. For more information, please visit nspharma.com. U.S. Media Contact: [email protected] SOURCE NS Pharma, Inc.