Scarring, or ‘fibrosis’, occurs when the normal repair mechanisms after injury do not work properly resulting in tissue becoming thicker and more stiff. This loss of elasticity subsequently affects the patient’s breathing as it makes it more difficult for the lungs to inflate. Fibrosis may occur across large parts of the lung, as is the case with the progressive condition of idiopathic pulmonary fibrosis and the cell-clumping condition of sarcoidosis. It may also occur in much smaller patches, such as around the borders of lung tumours.
Currently, the diagnosis of conditions involving fibrosis relies on a number of different measures, including lung biopsy, and available treatments following diagnosis are often limited. The early and accurate diagnosis of lung cancer may also be improved through detecting areas of scarring around suspected or confirmed lung cancer.
As part of this study, we will use a bespoke endoscopic pulmonary delivery device (called TLBC) to co-deliver microdose quantities of both FIB ONE and AZD1236 through a triple lumen (external diameter <2 mm) catheter guided by autofluorescence optical imaging to the distal alveolar regions. The novel TLBC is a single use sterile catheter with three lumens designed to fit into the accessory channel of a bronchoscope. We are also interested in whether a compound (AZD1236) that has been developed by Astra Zeneca can attenuate the emission of light from FIB ONE by blocking the process of fibrosis.
The principal aim of such studies include determining drug-target engagement in situ in vivo in diseased tissue in patients. This potential paradigm shift will enable increased confidence that the drug is ‘hitting the target’ or conversely provide early evidence that drug-target engagement is poor and potentially not worth pursuing.
We have so far recruited and dosed a total of 13 patients with a fibroproliferative lung condition as part of this proof-of-concept study. We have obtained some very encouraging data relating to the fluorescence profile of our FIB ONE Smartprobe and are now concentrating on whether a MMP inhibitor (AZD1236) can attenuate the FIB ONE signal and block MMP enzyme activity when administered directly into the human lung. To the best of our knowledge, this will be the first time that drug-target engagement has been visualised in real-time in the human lung.
Our proof-of-concept clinical study is currently investigating whether FIB ONE can detect scarring and whether our new detection system (Versicolour) can image FIB ONE following administration. Our approach is based on using Smartprobes coupled with miniature fibre-optic imaging bundles to access distal alveolar regions and transmit the image from the distal end of the fibre to the rest of the optics.