• Smoking cigarettes significantly damages the lungs and triggers the formation of senescent (dysfunctional) cells in lung tissue, contributing to the development of various lung diseases. 
  • In preclinical models, treatment with benidipine targets senescent lung cells and reduces lung damage caused by emphysema, a harmful lung disease characterized by the destruction of alveoli – tiny air sacs essential for gas exchange and lung function. 
  • Pending successful human trials, this could become a new way to undo some of the damage caused by smoking cigarettes. 

In a recent breakthrough study, scientists from the University of Lyon in France have identified a potential new treatment for lung diseases caused by cigarette smoke. The study, published in the journal Aging, demonstrates how benidipine can selectively eliminate smoking-induced senescent cells – dysfunctional cells that drive tissue aging. What’s more, in mice modeling emphysema, treatment with benidipine significantly reduces lung damage, further highlighting benidipine’s potential as a novel treatment for chronic lung diseases. 

The Harmful Effects of Cigarette Smoke

We all know smoking is bad for our lungs. But why? Cigarette smoke contains carcinogenic and stress-inducing compounds that damage and lead to mutations in DNA, disrupting cellular equilibrium. Notably, studies have linked cigarette smoke to the accumulation of senescent cells, a critical hallmark of aging. Moreover, senescent cells are known to release harmful inflammatory compounds, collectively referred to as the senescence-associated secretory phenotype (SASP), which further promote senescence and lung tissue deterioration. With this in mind, scientists have explored the use of compounds (senolytics) capable of targeting senescent cells as a means of slowing or even reversing lung disease progression caused by cigarette smoke. 

Breakthrough with Benidipine

Using the current library of FDA-approved drugs, the research team screened for compounds that specifically promote the death of senescent lung cells induced by cigarette smoke. Among the 134 potential candidates, the well-established blood pressure drug benidipine stood out, as it was able to significantly reduce human senescent lung cells in culture (isolated cells grown in a dish) without affecting non-senescent, healthy cells. This specificity was crucial, as it indicated the potential for targeted treatment with minimal side effects. 

After proving its effectiveness in isolated cells, the investigators proceeded to evaluate benidipine’s effects on mice with emphysema, a deadly lung disease heavily tied to cigarette smoking. After inducing emphysema in mice by injecting them with a compound called elastase, the researchers treated mice with 2.5 mg/kg of benidipine for five consecutive days every week for three weeks. 

The results demonstrated that treatment significantly mitigated lung damage typically caused by elastase, including increased alveolar size, which is known to impair the lung’s ability to give our blood oxygen and remove carbon dioxide. Upon further examination of lung tissue, the investigators noted that treatment decreased the activity of P21, a common marker of senescence, further confirming benidipine’s specificity for targeting senescent cells. 

(Palazzo et al., 2023 | Aging) Benidipine reduces the number of senescent lung cells and improves emphysema-related lung damage. (Left) Compared to untreated smoking-induced senescent cells (CSC-second bar), the percentage of dead senescent cells is significantly greater in those treated with benidipine (fourth bar). (Right) Compared to mice with lung emphysema (bottom left), which have large alveoli (white circles), those treated with benidipine (bottom right) have improved, smaller alveoli, as shown by the smaller white circles.

Repurposing Existing Drugs for Lung Disease Treatment

The University of Lyon’s research on benidipine exemplifies the potential of drug repurposing in treating chronic lung diseases like emphysema. This approach not only saves time and costs associated with drug development but also uncovers new applications for existing medications. The study’s findings suggest that benidipine could target and reduce senescent cells in smoke-damaged lungs, offering a promising new treatment strategy that goes beyond merely managing symptoms.

Future Prospects and Public Health Impact

This study opens the door for further research, including clinical trials to confirm benidipine’s efficacy and safety in treating lung diseases in humans. The broader implications for public health are significant, potentially reducing the global healthcare burden of chronic lung diseases caused by smoking. However, it is essential to remember that such treatments cannot replace preventative measures like smoking cessation for overall lung health.