Dr. Benoit Allard
Novel therapeutic strategy with alpha-1-antitrypsin-enriched nanoparticles
Background
Intravenous administration of α-1-antitrypsin (AAT) allows only 2-3% of AAT to enter the lungs and does not halt disease progression, but does reduce the rate of decline in lung density and function. However, it has no effect on exacerbation rates or health status. To improve patient care, AAT aerosolization has been explored. The inhaled route enables replacement therapy to reach the target site of action with higher AAT levels. Recently, the 1st randomized placebo-controlled clinical trial to investigate the effects of nebulized AAT concluded that, in AATD with frequent exacerbations, inhaled AAT for 50 weeks had no effect on time to 1st exacerbation, but may have altered the pattern of episodes. This clinical trial showed that inhaled AAT was safe and feasible in a large cohort of patients. We hypothesize that a new formulation of AAT would significantly enhance therapeutic benefits.
Our laboratory has developed Apolipoprotein A1 nanoparticles (A1NP), also known as reconstituted High-Density Lipoproteins (rHDLs), as therapeutic vectors. These nanoparticles have antioxidant, anti-endotoxin and anti-inflammatory properties. These protective effects have led several research teams to work on rHDL-based therapies administered intravenously, to treat cardiovascular diseases, cancers and neurodegenerative diseases. Our team demonstrated that native HDLs could be loaded with AAT and that i.v. injection of these nanoparticles significantly reduced elastase-induced pulmonary emphysema compared with HDLs or AAT alone in mice.
Here, we propose to evaluate the protectives combined effects of A1NP and AAT for the treatment of pulmonary emphysema in patients with AATD, to be tested in a preclinical model of emphysema by inhalation of AAT-enriched A1NP.
Aims
The main objective of the project is to provide a proof of concept for the innovative treatment of pulmonary emphysema in AATD by using inhalation of reconstituted apolipoprotein A1 nanoparticles enriched with AAT (A1NP-AAT).
- Production, characterization and biological function assessment of A1NP-AAT in vitro.
- To measure the biodistribution of A1NP-AAT following aerosolization in vivo.
- To evaluate the therapeutic potential of A1NP-AAT to prevent lung emphysema development.
Biography
Dr. Benoit Allard obtained his PhD in Cell Biology and Pathophysiology from the University of Bordeaux in 2013, at the Cardio-Thoracic Research Center of Bordeaux (INSERM U1045). Benoit Allard is currently an Associate Professor at the University of Reunion Island. He seeks to better understand the link between metabolic and respiratory diseases and how environmental factors can modify the progression of these diseases. He joined the DéTROI laboratory (INSERM U1188) in 2021 as a principal investigator in the therapeutic innovation research axis, after completing postdoctoral research in Bordeaux and at McGill University.