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Bronchial Thermoplasty: A Novel Therapeutic Approach to Severe Asthma

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Respirable antisense oligonucleotide (RASON) therapy for allergic asthma.

W J Metzger¹, J W Nyce

¹Section of Allergy, Asthma & Immunology, East Carolina University School of Medicine, Greenville, NC, USA.

Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy

|November 23, 2007

Summary

Respirable antisense oligonucleotides (RASONs) offer a novel approach to respiratory disease treatment by targeting gene expression in the lungs. This technology demonstrates efficient delivery and sustained therapeutic effects, paving the way for new asthma therapies.

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Area of Science:

Biotechnology
Pharmacology
Respiratory Medicine

Background:

Traditional respiratory drugs often target existing proteins, facing delivery challenges.
Gene expression modulation offers a targeted therapeutic strategy for respiratory diseases.

Purpose of the Study:

To introduce and evaluate respirable antisense oligonucleotides (RASONs) as a novel treatment for respiratory diseases.
To assess the efficacy, delivery, and pharmacokinetic profile of RASONs in a preclinical model.

Main Methods:

Development of respirable antisense oligonucleotides (RASONs) targeting messenger RNA (mRNA).
Administration of an adenosine A(1) antisense oligonucleotide to allergic rabbits with upregulated A(1) receptors.
Evaluation of desensitization to bronchoconstrictors and pharmacokinetic analysis of RASON distribution and excretion.

Main Results:

RASONs successfully attenuated gene expression by targeting mRNA in the lung.
Adenosine A(1) antisense oligonucleotide delivery resulted in sustained desensitization to bronchoconstrictors for nearly 7 days.
Low-dose RASON (EPI-2010) showed even lung distribution, no systemic metabolites, and primary urinary excretion.

Conclusions:

RASONs represent an efficient and effective method for delivering therapeutics directly to the peripheral lung.
This gene-targeting approach potently and selectively attenuates disease-associated gene expression.
RASON technology holds promise for treating bronchial asthma and other respiratory conditions.