title: Oligonucleotides: New therapeutic approaches for asthma and chronic obstructive pulmonary disease.
abstract: Asthma and COPD are significant lung diseases for which anti-inflammatories, including inhaled corticosteroids and leukotriene- targeted drugs, represent a key element of current therapy. Oligonucleotides comprise a diverse family of emerging drug candidates for the treatment of these diseases. There is a commonality in the chemistry of oligonucleotide drug molecules but, importantly, individual candidates are distinct in their molecular targets and also possess different mechanisms of action. Oligonucleotides may be divided in two groups based on their main mechanism of action: (i) RNA-targeting; and (ii) protein-targeting. Antisense oligonucleotides and siRNAs, both of which belong to the RNA-targeting group, and the immunostimulatory sequence-based drugs, which are members of the protein-targeting group, are progressing through clinical trials. In principle, the development of these agents is facilitated by a series of significant advantages, such as those associated with delivery to the lung via inhalation, and targeting to the site of action, resulting in reduced levels of systemic exposure. Although no oligonucleotide-based drug has been approved for the treatment of asthma or COPD, this class of compounds holds significant promise in the treatment of these two diseases. Several oligonucleotide drug candidates have been evaluated in the clinic with no significant adverse safety findings, while clinical proof of concept based on short-term inhalation protocols in challenge models in humans has also been established.
authors.affiliation: Topigen Pharmaceuticals Inc, 2901 Rachel Street East, Suite 13, Montreal, QC H1W 4A4, Canada. mark.pb123@sympatico.ca
authors.forename: Mark
authors.initials: M
authors.lastname: Parry-Billings
authors.forename: Nicolay
authors.initials: N
authors.lastname: Ferrari
authors.forename: Rosanne
authors.initials: R
authors.lastname: Seguin