In the lining of the airway, hair-like cilia sweep foreign matter, microbial contaminants, and mucus away. This clearance action is necessary for healthy lung function. Smoking, aging, and genetic mutations can  compromise cilia action in  the airway, leading to  common respiratory illnesses, such as chronic obstructive pulmonary disease (COPD) and asthma, which together affect about 500 million people worldwide. By restoring ciliary robustness in the  airway,  the Notch  antagonist  DAPT could  lessen  ongoing  lung  damage  from  these chronic diseases.

Technology Description

DAPT inhibits proteolytic cleavage of Notch, which is the transcription factor responsible for transforming epithelial cells —where cilia sprout—into mesenchymal cells. By pushing the balance toward ciliated  epithelial  tissue, DAPT  may  improve lung  clearance. In in vitro experiments with mouse tracheal tissue,  DAPT  increased the  number,  length,  and  beat frequency of cilia three fold. Beyond respiratory illness, DAPT may also be useful for treating hydrocephalus—retention of fluid in the ventricles of the brain—by increasing cilia action to help with drainage

Advantages

  • Entirely new way of treating common respiratory diseases
  • Cilia play a role in the function are many body systems, so DAPT could be broadly therapeutic

Applications

  • COPD
  • Primary ciliary dyskinesia (PCD)
  • Asthma
  • Emphysema
  • Cystic Fibrosis
  • Hydrocephalus

Stage of Development

ex vivo data

IP Status

PCT patent application filed

Innovator

Maliha Zahid, MD, PhD