TPI ASM8 reduces eosinophil progenitors in sputum after allergen challenge

Area of Science:

• Respiratory Medicine
• Immunology
• Pharmacology

Background:

• TPI ASM8 comprises two antisense oligonucleotides (AONs) targeting IL-3/IL-5/GM-CSF receptor beta chain (βc) and CCR3.
• Inhaled TPI ASM8 improves lung function and reduces sputum eosinophilia in asthmatics post-allergen challenge.

Purpose of the Study:

• To evaluate the efficacy of TPI ASM8 in reducing airway levels of haemopoietic progenitor cells in asthmatic subjects.
• To assess the impact of TPI ASM8 on airway inflammation markers following allergen exposure.

Main Methods:

• An open-label study involving 14 stable allergic mild asthmatics with early and late asthmatic responses.
• Subjects received placebo or TPI ASM8 (4 mg b.i.d. or 8 mg o.d.) for 4 days before allergen challenge.
• Sputum induction was performed pre-challenge and 7, 24 hours post-challenge for progenitor cell analysis.

Main Results:

• TPI ASM8 significantly reduced allergen-induced sputum eosinophils and early/late asthmatic responses (P<0.05).
• A significant reduction was observed in CD34(+) CCR3(+) cells (P=0.004) and CD34(+) IL-5Rα(+) cells (P=0.016).
• The proportion of CD34(+) cells expressing IL-5Rα also decreased significantly (P=0.036).

Conclusions:

• TPI ASM8 is safe and well-tolerated in mild asthmatics.
• Blocking CCR3 and βc receptors with TPI ASM8 inhibits airway eosinophil and progenitor cell accumulation post-allergen challenge.
• Inhibition of airway progenitor cell accumulation represents a novel therapeutic strategy for asthma.