Wedzicha’s talk provided a natural lead-in to a session titled, “New Approaches to Treating Old Diseases,” which was led off by Masahiro Sakagami of VCU. Sakagami discussed encouraging preclinical studies that suggest the possibility of repairing damage from emphysema, which is currently believed to be irreversible, by using salvianolic acid to elevate levels of vascular endothelial growth factor (VEGF).
VEGF deficiency is correlated with disease severity in emphysema, and increasing VEGF could hypothetically lead to alveolar repair and reversal of the disease, Sakagami said, though he cautioned that “translation to human disease state remains to be proven upon inhaled dosage form development.”
Philip Hansbro of the Centenary Institute and University of Technology, speaking on the topic of “Cross-Talk between Gut and Lung Microbiomes: Implications for Chronic Respiratory Disease,” challenged assumptions about the need to treat lung disease by treating the lung. Noting the association between gut bacteria and lung disease and the ability of the gut microbiome to change asthma phenotypes, he suggested that the gut might be a site for treatment of respiratory diseases. Attendees listened with interest and a certain amount of horror as Hansbro described the potential to improve chronic lung disease by modifying the gut microbiome through fecal transfer, or what he called “trans-poo-sions,” and/or diet.
The audience was also very engaged during the talk on “Cystic Fibrosis Gene Therapy: Improving Lung Gene Transfer Using Lentiviral Vectors” by
Eric Alton of Imperial College London. Alton described the use of a lentiviral vector pseudotyped with proteins from the Sendai virus, which is more efficient at transfecting the airway. Unlike most viral vectors, which cannot be dosed repeatedly due to immune response, the pseudotyped lentivirus has defied expectations and continued to work dose after dose.
According to Alton, a year-long study comparing gene transfer via the lentiviral vector versus placebo demonstrated stabilization of lung function in the active group of CF patients, while the placebo group had a decline in FEV1 over the year. Despite the apparent success, Alton said, “I do not think the magnitude of changes we saw and the robustness is sufficient, but this was just Wave 1.”
The next steps, Alton explained, will be helped along by an agreement between The UK Cystic Fibrosis Gene Therapy Consortium, Boehringer Ingelheim, and Oxford Biomedica for continued development of an inhaled lentiviral vector-based gene therapy formulation. He concluded by noting the importance of international cooperation in this work, pointing out that Brexit is not helpful.
