Safety, Pharmacokinetics and Pharmacodynamics of TNHH, a Novel Targeted Neutrophil-Inhibitory Hirulog Hybrid Glycoprotein, in Healthy Volunteers

Gou, Zhong Ping; Song, Zi Hui; Chen, Xiao‐Gang; Hu, Xiao; Wang, Ying; Fan, Kai; Cai, Yong; Li, Zheng

doi:10.1007/s40263-019-00628-0

Cited by 3 publications

(3 citation statements)

References 23 publications

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“…This drug is a recombinant glycoprotein, which binds selectively to thrombin and CD11b/CD18 integrin on neutrophils. The TNHH can be combined with Mac-1 molecules on the membrane of white blood cells to inhibit the adhesion, migration, invasion, and other activities of neutrophils (Gou et al, 2019). Although integrin and selectin blockers showed promising effects in animal studies, results from several human studies are disappointing (Németh, Sperandio, & Mócsai, 2020).…”

Section: Neutrophil Modulatory Moleculesmentioning

confidence: 99%

Neutrophils in respiratory syncytial virus infection: From harmful effects to therapeutic opportunities

Tahamtan

Besteman

Samadizadeh

et al. 2020

British J Pharmacology

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Respiratory syncytial virus (RSV) is an important infectious agent in infants and young children. In most cases, RSV infection only causes mild disease, but in some, it requires invasive ventilation. Although antiviral drugs are obvious candidates to treat viral illness, and some have shown antiviral effects in humans, antivirals such as GS-5806, ALX-0171 and ALS-8176 have not yet met their expectations. Since the inappropriate or dysregulated immune response against RSV leads to harmful immune pathology, a robust immune cascade is probably underway by the time patients reach the hospital. RSV infection is associated with a strong neutrophil influx into the airway. It not clear if these cells contribute to antiviral defence or to lung pathology. This article discusses the protective and harmful roles of neutrophils during RSV infection and provides an overview of mechanisms by which neutrophil function could be targeted to prevent tissue injury and preserve homeostasis.

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Section: Neutrophil Modulatory Moleculesmentioning

confidence: 99%

Neutrophils in respiratory syncytial virus infection: From harmful effects to therapeutic opportunities

Tahamtan

Besteman

Samadizadeh

et al. 2020

British J Pharmacology

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“…Although many developed countries have recorded a measure of success in stemming the rising incidence of stroke, in less developed countries poor health care systems are contributing to the overall global increase in incidence (Béjot, Daubail, & Giroud, 2016; Sadeghpour et al., 2020; Wasay, Khatri, & Kaul, 2014). The decrease in stroke incidence in developed countries may be partly attributed to the effective management of risk factors like hypertension as well as prompt medical attention to stroke patients enabling them to benefit from thrombolytic therapy which has a limited therapeutic time window (Donahue & Hendrikse, 2018; Gou et al., 2019; L. Huang et al., 2018). Although tissue plasminogen activator (tPA) is considered the gold standard treatment for ischemic stroke, one of its side effects is the enhancement of inflammatory response in brain capillaries and subsequently neuronal cell damage after stroke (Amani, Habibey, et al, 2019; Amani, Mostafavi, et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Prophylaxis with a multicomponent nutraceutical abates transient cerebral ischemia/reperfusion injury

et al. 2020

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“…This drug is a recombinant glycoprotein, which binds selectively to thrombin and CD11b/CD18 integrin on neutrophils. The TNHH can be combined with Mac-1 molecules on the membrane of white blood cells to inhibit the adhesion, migration, invasion, and other activities of neutrophils (Gou et al, 2019). Although integrin and selectin blockers showed promising effects in animal studies, several human studies' results are disappointing (Németh et al, 2020).…”

Section: Neutrophil Modulatory Moleculesmentioning

confidence: 99%

The local innate immune response during severe respiratory syncytial virus infection

Besteman¹

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REspiRaToRy syncyTial viRus is a majoR causE of childhood pnEumonia woRldwidERespiratory syncytial virus (RSV) was first identified as chimpanzee coryza agent, in 1955, in chimpanzees with respiratory complaints. 1 In 1957 it was isolated from the lungs of infants with respiratory illness. 2 Nowadays, RSV is recognized as one of the most important pathogens identified in respiratory tract infections (RTI), especially in young infants, resulting in significant morbidity and mortality worldwide. 3 In children under five, RSV is estimated to lead to 3.2 million hospital admission and 125 000 deaths per year. 3, 4 The clinical picture varies from mild upper respiratory tract symptoms, such as a runny nose and otitis, to extensive infection and inflammation of the lower airways, called bronchiolitis, leading to coughing and respiratory distress. In 2-12% of the children admitted to the hospital with RSV bronchiolitis the disease progresses to life threatening respiratory distress warranting invasive mechanical ventilation at the pediatric intensive care unit (PICU). 3, 5 Despite over 60 years of research there is still no worldwide accessible and affordable vaccine or drug available. 6 Severe RSV disease can be prevented by palivizumab, a monoclonal antibody (mAb) against the fusion (F) protein of RSV. 7 However, this is only available for high-risk children in developed countries due to excessive costs. Ribavirin is the only registered antiviral therapeutic registered for RSV and lacks overall effectiveness. 8 Merely good hygiene and supportive measures such as supplemental oxygen supply or mechanical ventilation can aid this vulnerable group of patients. Due to a lack of resources in large parts of the world, over 90% of RSV-related childhood mortality occurs in low income countries. 4, 9 Promising preventive strategies currently being developed and tested in clinical trials include maternal immunization to protect infants, infant mAb prophylaxis with extended half-life (Nirsevimab), and the development of live-attenuated RSV vaccines. 6, 10-13 (Figure 1) Advances in understanding RSV disease pathology will aid mAb and RSV vaccine development.

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Safety, Pharmacokinetics and Pharmacodynamics of TNHH, a Novel Targeted Neutrophil-Inhibitory Hirulog Hybrid Glycoprotein, in Healthy Volunteers

Cited by 3 publications

References 23 publications

Neutrophils in respiratory syncytial virus infection: From harmful effects to therapeutic opportunities

Neutrophils in respiratory syncytial virus infection: From harmful effects to therapeutic opportunities

Prophylaxis with a multicomponent nutraceutical abates transient cerebral ischemia/reperfusion injury

The local innate immune response during severe respiratory syncytial virus infection

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