PRESS RELEASE – Targeting inflammation to prevent preterm birth

A molecule named rytvela decreases uteroplacental inflammation, prevents preterm birth and improves perinatal outcomes through biased antagonism of the IL-1 receptor (functional selectivity)

Preterm birth (PTB) affects more than 10% of pregnancies worldwide and is the leading cause of neonatal mortality. Current treatments target myometrial contractility and are largely ineffective at improving perinatal outcomes. Myometrial contractions represent the final stage of a long process of uterine activation orchestrated by in utero inflammatory processes. If triggered prematurely (e.g. by infection), inflammation inevitably leads to preterm labor, with the timing of onset being inversely correlated with adverse neonatal outcomes and associated lifelong complications. Interleukin-1 (IL-1) is a major proinflammatory cytokine that has been firmly linked to human PTB and fetal organ injuries.

In a review article published in Current Pharmaceutical Design, Nadeau-Vallée et al. summarize the most recent evidence on the efficacy of molecules that target IL-1 to prevent PTB. Of all inhibitors of IL-1, the selective IL-1 receptor inhibitor rytvela (all-d heptapeptide) stands out preclinically as superiorly potent, effective, and safe in the prevention of PTB and its consequences. “Rytvela exerts benefits in decreasing uteroplacental inflammation, decreasing premature birth, prolonging gestation, increasing fetal survival, and improving fetal and neonatal outcome including that of the neurodevelopment” says Dr. Sylvain Chemtob, neonatologist, researcher, and principal author of the article. “Other than preventing preterm labor, rytvela also decreases inflammation inside the fetal compartment and in fetal organs, which is of significant importance because numerous neonatal conditions have been linked to inflammation independent of prematurity. Antenatal treatment with rytvela results in normalisation of lung, intestine and cerebral pathology scores during development and at adulthood”.

The effects of rytvela have been validated in vitro in murine and human uterine and immune cells, and in vivo in numerous murine models of PTB. Mechanistically, rytvela binds on a site remote from the binding site of IL-1 and act as a biased ligand by selectively inhibiting the p38/JNK/AP-1 pathway while preserving the activity of transcription factor NF-kB. This innovative mechanism of action may help decrease adverse effects (e.g. immunosuppression) which are particularly undesirable in the context of pregnancy.

Read more here: http://www.eurekaselect.com/155176

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New Issue :: Current Pharmaceutical Design Volume 23, Issue 34

Current Pharmaceutical Design publishes timely in-depth reviews and research articles from leading pharmaceutical researchers in the field, covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area guest edited by an acknowledged authority in the field.

Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

cpd-14-16

Articles from the journal Combinatorial Chemistry & High Throughput Screening Volume 20, Issue 9

                          For details on the articles, please visit this link :: http://bit.ly/2n9HAyC

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PRESS RELEASE – 2-hydroxypropyl-β-cyclodextrins and blood-brain barrier in Niemann-Pick Disease type C1

This article by Dr. Pericles Calias is published in Current Pharmaceutical Design, Volume 23 , 2017

A new data review concludes that 2-hydroxypropyl-β-cyclodextrin (HPβCD) does not cross the blood-brain barrier (BBB) in therapeutically relevant amounts to address the neurological manifestations of Niemann-Pick Disease Type C1 (NPC1). These manifestations vary with age of onset and include delay in developmental motor milestones, gait problems, falls, clumsiness, vertical supranuclear gaze palsy, cerebellar ataxia, dysarthria, dysphagia and progressive dementia . Based upon physicochemical properties, findings in animal models, early clinical studies, and patient case reports, the evidence to date suggests that HPβCD does not cross the BBB in therapeutically relevant amounts in the NPC1 setting. Direct administration to the central nervous system (CNS) would be expected to provide the greatest NPC1 neurological efficacy and is supported by a phase 1/2a clinical study .

The review was published online in the latest issue of Current Pharmaceutical Design.

NPC1 is an autosomal-recessive, rare lysosomal storage characterized by progressively debilitating and ultimately fatal neurological manifestations. Clinical trials of different HPβCD agents are currently underway and the route of administration is an important point of consideration for the anticipated results of these trials with regard to safety, tolerability and efficacy in the NPC1 population.

Cyclodextrins are complex mixtures of different chemical species and different cyclodextrin products are therefore not the same as one another. When administering drugs directly to the CNS, it is important that the agent being administered is highly purified and well characterized to avoid introducing any contaminants and/or unknown agents that could adversely affect neurological development and/or function. Currently, VTS-270 is the only specific and well-characterized mixture of HPβCD, with a tightly controlled molar substitution specification and a defined molecular “fingerprint” of the different chemical species present in the mixture based on Kleptose® HPB (Roquette Pharma, France).

 

The article is open access and its full text can be downloaded from here: http://www.eurekaselect.com/156484

HIGHLIGHTED ARTICLE – TARGETING HUMAN ASTROCYTES’ CALCIUM-SENSING RECEPTORS FOR TREATMENT OF ALZHEIMER’S DISEASE – CURRENT PHARMACEUTICAL DESIGN

CPD-23-46-Ubaldo Armato

To access the article, please visit: http://www.eurekaselect.com/154081

Testimonial by Yuanyuan Wang!

Yuanyuan Wang

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TESTIMONIAL BY GUIDO RUBBOLI!

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