Tag: Therapeutic

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Researchers identify hCRTh2 protein as possible therapeutic target for asthma – News-Medical.net

Researchers identify hCRTh2 protein as possible therapeutic target for asthma
News-Medical.net
Patients with asthma have chronic lung inflammation that results in sporadic narrowing of the airways and difficulty breathing. Symptoms and severity are variable among individuals; however, the cells and inflammatory factors that trigger asthmatic …

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Differential gene network analysis for the identification of asthma-associated therapeutic targets in allergen-specific T-helper memory responses.

Differential gene network analysis for the identification of asthma-associated therapeutic targets in allergen-specific T-helper memory responses.

BMC Med Genomics. 2016;9(1):9

Authors: Troy NM, Hollams EM, Holt PG, Bosco A

Abstract
BACKGROUND: Asthma is strongly associated with allergic sensitization, but the mechanisms that determine why only a subset of atopics develop asthma are not well understood. The aim of this study was to test the hypothesis that variations in allergen-driven CD4 T cell responses are associated with susceptibility to expression of asthma symptoms.
METHODS: The study population consisted of house dust mite (HDM) sensitized atopics with current asthma (n?=?22), HDM-sensitized atopics without current asthma (n?=?26), and HDM-nonsensitized controls (n?=?24). Peripheral blood mononuclear cells from these groups were cultured in the presence or absence of HDM extract for 24 h. CD4 T cells were then isolated by immunomagnetic separation, and gene expression patterns were profiled on microarrays.
RESULTS: Differential network analysis of HDM-induced CD4 T cell responses in sensitized atopics with or without asthma unveiled a cohort of asthma-associated genes that escaped detection by more conventional data analysis techniques. These asthma-associated genes were enriched for targets of STAT6 signaling, and they were nested within a larger coexpression module comprising 406 genes. Upstream regulator analysis suggested that this module was driven primarily by IL-2, IL-4, and TNF signaling; reconstruction of the wiring diagram of the module revealed a series of hub genes involved in inflammation (IL-1B, NFkB, STAT1, STAT3), apoptosis (BCL2, MYC), and regulatory T cells (IL-2Ra, FoxP3). Finally, we identified several negative regulators of asthmatic CD4 T cell responses to allergens (e.g. IL-10, type I interferons, microRNAs, drugs, metabolites), and these represent logical candidates for therapeutic intervention.
CONCLUSION: Differential network analysis of allergen-induced CD4 T cell responses can unmask covert disease-associated genes and pin point novel therapeutic targets.

PMID: 26922672 [PubMed – as supplied by publisher]

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New Therapeutic Program Leader to Take Over Asthma, Other Conditions at Knopp … – Lung Disease News


Lung Disease News

New Therapeutic Program Leader to Take Over Asthma, Other Conditions at Knopp …
Lung Disease News
Dexpramipexole is an oral, small molecule medicine candidate, currently in development for the treatment of asthma, amyotrophic lateral sclerosis (ALS), and other conditions associated with eosinophils — white blood cells of the immune system …

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Therapeutic potential of soluble guanylate cyclase modulators in neonatal chronic lung disease.

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Therapeutic potential of soluble guanylate cyclase modulators in neonatal chronic lung disease.

Am J Physiol Lung Cell Mol Physiol. 2015 Oct 2;:ajplung.00333.2015

Authors: Wagenaar GT, Hiemstra PS, Gosens R

Abstract
Supplemental oxygen after premature birth results in aberrant airway, alveolar and pulmonary vascular development with an increased risk for bronchopulmonary dysplasia (BPD), and development of wheeze and asthma, pulmonary hypertension and COPD in survivors. Although stimulation of the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic GMP (cGMP) signal transduction pathway has significant beneficial effects on disease development in animal models, so far this could not be translated to the clinic. Oxidative stress reduces the NO-sGC-cGMP pathway by oxidizing heme-bound sGC, resulting in inactivation or degradation of sGC. Reduced sGC activity and/or expression is associated with pathology due to premature birth, oxidative stress-induced lung injury, including impaired alveolar maturation, smooth muscle cell (SMC) proliferation and contraction, impaired airway relaxation and vasodilation, inflammation, pulmonary hypertension, right ventricular hypertrophy and an aggravated response towards hyperoxia-induced neonatal lung injury. Recently, Britt et al. (10) demonstrated that histamine-induced Ca2+ responses were significantly elevated in hyperoxia-exposed fetal human airway SMC’s compared to normoxic controls, and that this hyperoxia-induced increase in the response was strongly reduced by NO-independent stimulation and activation of sGC. These recent studies highlight the therapeutic potential of sGC modulators in the treatment of preterm infants for respiratory distress with supplemental oxygen. Such treatment is aimed at improving aberrant alveolar and vascular development of the neonatal lung, and preventing the development of wheezing and asthma in survivors of premature birth. In addition, these studies highlight the suitability of fetal human airway SMC’s as a translational model for pathological airway changes in the neonate.

PMID: 26432873 [PubMed – as supplied by publisher]

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Severe asthma: Gallopamil confirmed as a therapeutic approach – Medical Xpress


Medical Xpress

Severe asthma: Gallopamil confirmed as a therapeutic approach
Medical Xpress
A team of Inserm researchers from the Cardio-Thoracic Research Centre of Bordeaux (Inserm/University of Bordeaux and Bordeaux University Hospital) has demonstrated the clinical efficacy of gallopamil in 31 patients with severe asthma. This chronic …

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CXCR4 Antagonism as a Therapeutic Approach to Prevent Acute Kidney Injury.

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CXCR4 Antagonism as a Therapeutic Approach to Prevent Acute Kidney Injury.

Am J Physiol Renal Physiol. 2014 Jul 30;

Authors: Zuk A, Gershenovich M, Ivanova Y, MacFarland RT, Fricker SP, Ledbetter SR

Abstract
We examined whether antagonism of the CXCR4 receptor ameliorates the loss of renal function following ischemia-reperfusion. CXCR4 is ubiquitously expressed on leukocytes, known mediators of renal injury, and on bone marrow hematopoietic stem cells (HSC). Plerixafor (AMD3100, Mozobil ) is a small molecule CXCR4 antagonist that mobilizes HSCs into the peripheral blood and also modulates the immune response in in vivo rodent models of asthma and rheumatoid arthritis. Treatment with plerixafor before and after ischemic clamping ameliorated kidney injury in a rat model of bilateral renal ischemia-reperfusion. Serum creatinine and blood urea nitrogen were significantly reduced 24 hours after reperfusion, as was tissue injury and cell death. Plerixafor prevented the renal increase in the pro-inflammatory chemokines CXCL1 and CXCL5 and the cytokine IL-6. Flow cytometry of kidney homogenates confirmed the presence of significantly fewer leukocytes with plerixafor treatment; additionally, myeloperoxidase activity was reduced. AMD3465, a monocyclam analogue of AMD3100, was likewise renoprotective. Four weeks post-reperfusion, long-term effects included diminished fibrosis, inflammation and ongoing renal injury. The mechanism by which CXCR4 inhibition ameliorates AKI is due to modulation of leukocyte infiltration and expression of pro-inflammatory chemokines/cytokines, rather than a HSC mediated effect. The data suggest that CXCR4 antagonism with plerixafor may be a potential option to prevent AKI.

PMID: 25080523 [PubMed – as supplied by publisher]

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