Asthma translational medicine: report card

Area of Science:

• Immunology
• Pharmacology
• Respiratory Medicine

Background:

• Scientific research in asthma has predominantly focused on airway inflammation.
• This has led to a detailed understanding of T cell and eosinophil involvement post-antigen challenge.
• Asthma research models often equate the disease with T helper 2 cell-mediated responses.

Purpose of the Study:

• To evaluate the translational success of asthma research models.
• To assess the clinical efficacy of therapies targeting airway inflammation.
• To discuss the need for re-evaluating the focus of asthma research and drug discovery.

Main Methods:

• Review of clinical results from 39 compounds and biologics.
• Analysis of therapies acting on 23 different molecular targets.
• Evaluation of Phase 2 "proof-of-concept" clinical trial data.

Main Results:

• While 6 of 39 tested drugs showed qualified success, none provided broad benefit to asthma sufferers.
• Therapies highly effective in decreasing airway inflammation in animal models translated poorly to human clinical trials.
• The current research paradigm has yielded disappointing clinical success rates.

Conclusions:

• The long-standing focus on airway inflammation in asthma research may not be sufficient for developing broadly effective treatments.
• A re-evaluation of the underlying scientific and immune paradigms driving asthma drug discovery is warranted.
• Future efforts should explore alternative targets and research models to better address the heterogeneity of asthma.