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Efficacy and Safety of ASM8: An Anticytokine Oligonucleotide Combination in Allergic Asthmatics

Gauvreau GM, O'Byrne PM.

RDD Europe 2011. Volume 1, 2011: 29-40.

Abstract:

Antisense oligonucleotides (AONs) can be used as a therapy to down-regulate the transcription of specific proteins. There are several AONs in clinical development for treatment of asthma. TPI-ASM8 consists of two synthetic AONs which target the IL-3/5/GM-CSF common beta receptor chain (βc) and the eotaxin receptor, CCR3. Preclinical studies using antigen challenge in rats demonstrated that blocking βc or CCR3 reduced the target mRNA and protein expression in lungs, and also reduced the influx of eosinophils to the airways. The objective of this study was to examine the safety of nebulized TPI-ASM8 in allergic mild asthmatic subjects, and to determine the effects on allergen-induced airway inflammation, target gene expression, and early and late phase asthmatic responses. We hypothesized that TPIASM8 would block eosinophil migration to the airways by down-regulating expression of CCR3 and βc and that this would in turn inhibit allergen-induced physiological responses that are associated with eosinophilic inflammation. The results demonstrated that TPI-SM8 downregulated the expression of the target mRNA, blocked the influx of eosinophils into the airways post-allergen challenge, and attenuated the late asthmatic response. We concluded that TPI-ASM8 is safe and well tolerated at all dose levels studied, and that these results supported TPI-ASM8 as a once per day therapy for treatment of allergic asthma.