Randomized, Double-Blind, Placebo Controlled First in Human Study of Inhaled AIR645, an IL-4Rα Oligonucleotide, in Healthy Volunteers.

Hodges, Matt; Castelloe, Erin; Chen, A; Rs, Geary; Karras, JG; Shapiro, D.; Yeung, Biu; Yu, Rongbin; Gregory, SA

doi:10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a3640

Cited by 14 publications

(8 citation statements)

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“…Based on prior experience with the IL-4Rα program [20], we estimate the human dose of ASO to give us an approximately 70% reduction of ENaC mRNA is 12 mg delivered to the lung. In a previous study with inhaled ASOs in human, a dose of 30 mg was successfully administered with no safety issues [37]. In addition, ASO aerosol delivery has been shown to be well tolerated in humans as well as rodents and non-human primates [19][20][21].…”

Section: Discussionmentioning

confidence: 99%

Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice

Crosby

Zhao

Jiang

et al. 2017

Journal of Cystic Fibrosis

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Section: Discussionmentioning

confidence: 99%

Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice

Crosby

Zhao

Jiang

et al. 2017

Journal of Cystic Fibrosis

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“…Results from a phase I study evaluating the safety, tolerability and pharmacokinetics of once-weekly treatment with inhaled AIR645 in healthy volunteers demonstrated no serious adverse events or doselimiting toxicities following a single or multiple doses of the drug [67]. Prolonged local exposure was observed in the airways, with a half-life of ,5 days in induced sputum, which was independent of the dose.…”

Section: Isis Altairmentioning

confidence: 96%

Investigational therapeutics targeting the IL-4/IL-13/STAT-6 pathway for the treatment of asthma

Oh¹,

Geba²,

Molfino³

2010

European Respiratory Review

235

164

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Asthma is a complex, persistent, inflammatory disease characterised by airway hyperresponsiveness in association with airway inflammation. Studies suggest that regular use of high-dose inhaled corticosteroids and long-acting bronchodilators or omalizumab (a humanised monoclonal antibody that binds to immunoglobulin E and is often used as next-step therapy) may not be sufficient to provide asthma control in all patients, highlighting an important unmet need. Interleukin-4, interleukin-13, and the signal transducer and activator of transcription factor-6 are key components in the development of airway inflammation, mucus production, and airway hyperresponsiveness in asthma. Biological compounds targeting these molecules may provide a new therapeutic modality for patients with uncontrolled severe asthma. The purpose of this review is to summarise current studies of compounds targeting the interleukin-4/interleukin-13 pathway and to provide a rationale for the development of such compounds for this use.

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“…AIR 645 (Altair Therapeutics, San Diego, CA, USA) is a 2′‐O‐methoxyethyl ‘2‐MOE Gapmer’ antisense oligonucleotide that targets the mRNA encoding IL‐4Rα and prevents its translation into a functional protein. A Phase I clinical trial of nebulized AIR 645 in healthy volunteers demonstrated low systemic absorption and no severe adverse events (14). A Phase IIa clinical trial in mild allergic asthmatics was recently completed, although no results have been reported yet (15).…”

Section: Blocking Critical Th2 Cytokinesmentioning

confidence: 99%

Immune modulation for treatment of allergic disease

Nguyen

Casale

2011

Immunological Reviews

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Immune modulation for treatment of allergic diseases aims to decrease the pathologic immune response rather than to cause a return to an immunologically naive or unresponsive state. Our expanding knowledge of innate and adaptive immune responses at the molecular level has led to development of immunomodulators for several allergic diseases, particularly asthma, allergic rhinitis, and eosinophilic esophagitis. Although successful immune modulation in mouse models of allergic disease have often failed to translate into significant results in human clinical trials, much has been learned about the pleotropic nature of cytokines and their effector mechanisms and of the varied phenotypes of allergic disease. We examine strategies of immune modulation in allergic diseases that have undergone human clinical trials, all with the common goal of decreasing the T-helper 2 (Th2) response, but through different mechanisms: blocking critical Th2 cytokines, inhibiting Th2 cytokine synthesis, blocking critical Th2 effector molecules, inhibiting important cells in the Th2 response, and stimulating Th1 responses. Therapies directed against specific effector molecules, such as immunoglobulin E and prostaglandin D2, hold promise in immune modulation of allergic disease, as do targeting the IL-4/IL-13 receptor and augmenting Th1/Th2 balance with Toll-like receptor agonists.

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Randomized, Double-Blind, Placebo Controlled First in Human Study of Inhaled AIR645, an IL-4Rα Oligonucleotide, in Healthy Volunteers.

Cited by 14 publications

References 0 publications

Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice

Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice

Investigational therapeutics targeting the IL-4/IL-13/STAT-6 pathway for the treatment of asthma

Immune modulation for treatment of allergic disease

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