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Using “good cholesterol” as a therapeutic vector for treating the lungs

07 May 2014 | By INSERM (Newsroom) | Circulation, metabolism, nutrition

One of the major challenges for therapeutic science is to optimise the accurate distribution of drugs in the affected organs. Targeted delivery methods are needed to accomplish this.

In a new study published in The American Journal of Respiratory Cell and Molecular Biology, Olivier Meilhac’s team (Inserm Unit 1148, the “Laboratory for Vascular Translational Science,” in collaboration with Inserm Unit 1152, “Physiopathology and Epidemiology of Respiratory Diseases”) addressed the transport capability of HDLs (high density lipoproteins, commonly known as “good cholesterol”). These naturally occurring nanoparticles carry cholesterol, but may also be loaded with drugs or other protective molecules. Their study shows that intravenously injected HDLs help to convey a therapeutic drug, alpha-1 antitrypsin, to the lungs, to reduce pulmonary emphysema.

Pulmonary emphysema is characterised by progressive destruction of the pulmonary alveoli, which ultimately leads to respiratory failure. The cause: inflammatory cells that secrete an enzyme, elastase, which is involved in the development of these lesions. This mechanism is especially involved in patients with a genetic defect in another enzyme, alpha-1 antitrypsin (AAT), a natural inhibitor of elastase. This frequent genetic disorder affects 1 in 3,000 people, and is responsible for approximately 1% of emphysema cases.

The treatment currently offered to patients with emphysema who are deficient in AAT involves intravenous administration of AAT, with the challenge mentioned earlier, namely: how to reach the lungs efficiently? This work shows that in mice, loading AAT onto HDLs improves its delivery to the lungs, where it can limit elastase-induced damage, compared with the standard treatment.

Pulmonary emphysema is present to different degrees in patients with chronic obstructive pulmonary disease (COPD), a very common (5-10% of the adult population) and serious disease (16,000 deaths per year), which particularly affects smokers. The researchers believe that these “therapeutic HDLs” may be a useful avenue for improving the treatment of COPD.

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Researcher Contact

Olivier Meilhac
Unité Inserm 1148 “Laboratoire de recherche vasculaire translationnelle”
Email : rf.mresni@cahliem.reivilo
Tel : 06 93 40 65 45


High Density Lipoproteins potentiate alpha-1 antitrypsin therapy in elastase-induced pulmonary emphysema

Juan-Antonio Moreno, Almudena Ortega-Gomez, Alfonso Rubio-Navarro, Liliane Louedec, Benoit Ho-Tin-Noé, Giuseppina Caligiuri, Antonino Nicoletti, Angelique Levoye, Laurent Plantier, and Olivier Meilhac
Am J Respir Cell Mol Biol. First published online 01 May 2014