SUMMARY
- Airway remodeling induced by asthma and fibrosis promotes reduced responsiveness to currently available therapies. As such, there is an urgent need for the development of novel treatments that target the underlying molecular mechanisms of tissue remodeling in asthma and fibrosis.
- The inventors discovered a novel class of organic molecule that blocks the pathogenic transition of fibroblasts to fibrosis inducing myofibroblasts. Furthermore, these organic molecules block the accumulation of smooth muscle contractile proteins and extracellular matrix in the lung, which are hallmarks of fibrosis.
- The invention is a new class of small molecules called remodilins that prevent the underlying tissue remodeling of pulmonary fibrosis and asthma. Inhibiting tissue remodeling is critical since it limits the efficacy of currently available therapeutics.
- In Vivo proof of concept experiments in bleomycin induced pulmonary fibrosis mouse models showed remodilins reduced gene expression associated with pathogenic fibroblast signaling pathways, and reduced collagen buildup in the lungs.
FIGURE
A) Airway remodeling is reduced in remodelin-treated mice with experimental allergic asthma, as reflected in significantly lower MYH11 immunostain-positive airway smooth muscle area normalized to epithelial length compared with 20% Solutol (vehicle), in the large airways.
ADVANTAGES
ADVANTAGES
- First-in-class small molecules
- Could be aerosolized for direct drug delivery
- Inhibits airway remodeling
- Multiple lead compounds available
APPLICATIONS
- Asthma therapy
- Pulmonary fibrosis therapy (potentially expandable to other fibrosis types)
August 2, 2019
In vivo proof of concept (Asthma and Pulmonary Fibrosis)
Patent Pending
Licensing,Co-development
Julian Solway
- Preliminary toxiciology studies