NFL-101 AND SMOKING CESSATION
What if tobacco became the best way to quit smoking? That's the idea behind NFL Biosciences' botanical drug-candidate NFL-101. The latter is derived from a nicotine-free allergenic tobacco extract, originally developed by the Institut Pasteur in France in the 1970s, to desensitize tobacco factory workers who had developed allergies to the plant through repeated handling. Since then, NFL-101 has successfully passed clinical trials (phases 1 and 2), but its mechanism of action remains to be understood. Indeed, despite extensive research on NFL-101 as an immune therapy for smoking cessation in humans, the immune response to NFL-101 and its ability to induce significant changes in brain function remain to be demonstrated.
PET TO UNDERSTAND THE EFFECT OF NFL-101 ON BRAIN ACTIVITY
In the present study, [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) PET imaging was used to monitor changes in brain function associated with the development of withdrawal in a mouse model of chronic tobacco smoke exposure, and then to demonstrate the central effects of NFL-101 treatment. The authors observed that cerebral metabolism during smoking cessation was reduced in the thalamus, a region rich in nicotinic receptors, known for its role in tobacco addiction, and in the brainstem. In treated mice, a single dose of NFL-101 significantly restored normal glucose metabolism in the thalamus. A humoral immune response to NFL-101 with the production of specific circulating IgG antibodies was observed in these animals. The authors also demonstrated a cellular immune response to the drug in vitro, resulting in the activation of human "Natural Killer" T lymphocytes.
Using a robust preclinical model of smoking exposure-withdrawal, this [18F]FDG PET imaging study highlights the ability of NFL-101 to restore normal metabolic activity in the brain region associated with the need to smoke, and suggests a communication between the immune and central nervous systems, i.e. a different mode of action from that of current smoking cessation drugs, primarily targeting nicotinic receptors. It argues in favor of evaluating innovative smoking cessation therapies using [18F]FDG PET imaging.
Contact : sebastien.goutal@universite-paris-saclay.fr ou n.tournier@universite-paris-saclay.fr