12:00 AM
Apr 02, 2015
 |  BC Innovations  |  Targets & Mechanisms

Breathing through bone drugs

How Merck's osteoporosis drug alendronate could be repurposed for COPD

Reversing or halting progressive airway damage is still the biggest challenge in COPD, but a study from Japan suggests a subclass of osteoporosis drugs could offer a new way to tackle the disease that takes advantage of the compounds' ability to suppress macrophages. The strategy capitalizes on new thinking that alveolar macrophages play a dominant pathological role in COPD, but some researchers question whether suppressing the cells will remove a key mechanism for preventing infection in the lungs.

In chronic obstructive pulmonary disease (COPD), the characteristic decrease in airflow is caused by inflammation, which causes the hallmark breakdown of elastin and destroys the integrity of the alveolar walls.

Although many types of immune cells infiltrate the airspace in COPD in response to injury, alveolar macrophages have recently been implicated as the main drivers of the disease. That is a shift from the previous dogma that neutrophils were the key contributors to COPD pathology, and that the role of macrophages was primarily to protect against infection in the lung.

Now, it is recognized that accumulation and activation of macrophages causes neutrophil infiltration and activation, and triggers chemokine and cytokine production. Together, the effects lead to the mucus hypersecretion, alveolar wall destruction and bacterial colonization that characterize the lung pathology in the disease. (See Figure: Macrophage-driven COPD)

Despite the changed thinking, no COPD therapeutics have been designed to specifically inhibit alveolar macrophages.

Masahiko Kurabayashi and colleagues wanted to find a way to suppress the macrophages without affecting other immune cells in the lung, or other macrophages in the rest of the body. Kurabayashi is chief professor of medicine and biological science at Gunma University Graduate School of Medicine.

Bisphosphonate drugs have been shown to induce apoptosis of mouse macrophage cell lines and safety studies using aerosolized versions of the drugs have already been conducted. While there was no information about their activity against alveolar macrophages, Kurabayashi's team hypothesized the drugs could provide a tractable option for inhibiting the...

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