Thailand Doctors Discover Potential Gene Therapy for Pulmonary Fibrosis

Thailand Doctors: Understanding Pulmonary Fibrosis and Its Growing Impact
Pulmonary fibrosis is a severe lung disease that progressively scars lung tissue, making it difficult for the body to absorb oxygen. It affects millions worldwide and has become more prevalent following the COVID-19 pandemic. The disease, which leads to a decline in lung function, has no definitive cure, with most treatments only managing symptoms rather than reversing the condition. The median survival rate after diagnosis is about three years, and severe cases have an annual mortality rate of 50%.


Thailand Doctors Discover Potential Gene Therapy for Pulmonary Fibrosis

A new breakthrough from researchers in Thailand, however, offers hope. Thailand Doctors from Chulalongkorn University and Chiang Mai University have identified a novel gene therapy that may help reverse the effects of pulmonary fibrosis. This Medical News report explores their findings, which focus on a genetic approach that targets the underlying causes of lung fibrosis.
 
The Role of Cellular Senescence in Pulmonary Fibrosis
Over the years, medical scientists have identified several factors that contribute to pulmonary fibrosis, including genetic mutations, immune system disorders, and environmental exposures. However, one key factor that has gained significant attention is cellular senescence - the process by which cells lose their ability to divide and function normally. Senescent cells accumulate in lung tissues, promoting excessive fibrosis and inflammation.
 
The team of Thai researchers focused on a specific protein known as High Mobility Group Box 1 (HMGB1), which plays a role in DNA repair and cellular health. Their research has demonstrated that a specific portion of this protein, called Box A, has the potential to reverse cellular senescence and restore normal lung function.
 
The Study’s Approach and Methodology
The study was conducted using a rat model to evaluate the effects of Box A gene therapy on bleomycin-induced pulmonary fibrosis. Bleomycin, a chemotherapy drug known to cause lung damage, was used to mimic pulmonary fibrosis in rats. Thirty-six male Wistar rats were divided into six groups, including control and treatment groups that received Box A therapy for six or eight weeks.
 
The Box A therapy was delivered using a specialized plasmid coated with calcium-phosphate nanoparticles, allowing it to penetrate lung tissue effectively. The researchers measured several key indicators of pulmonary fibrosis, including the accumulation of fibrous tissue, the presence of senescent cells, and the production of surfactant protein C, which is essential for lung function.
 
Key Findings of the Study
One of the most remarkable results of the study was the significant reduction in fibrotic tissue following Box A therapy. In untreated fibrotic rats, fibrous tissue covered approximately 18.74% of the lung area. However, after Box A treatment, this number dropped to just 3.45%, making it comparable to the control group.

In addition to reducing fibrotic deposits, Box A also lowered the number of senescent cells in lung tissues. The percentage of senescent cells in untreated fibrotic rats was recorded at 3.74%, whereas those treated with Box A showed a drastic decrease to 0.89%.
 
Another critical finding was the increase in surfactant protein C production, which is essential for maintaining lung elasticity and function. Before treatment, surfactant protein levels were at 3.60%. Following eight weeks of Box A therapy, levels rose to 6.82%, indicating a restoration of lung function.
 
How Box A Gene Therapy Works
The mechanism behind Box A therapy involves targeting cellular senescence at a genetic level. Box A plays a crucial role in protecting DNA, preventing damage, and reducing stress within cells. By introducing the Box A plasmid into lung tissues, the therapy helps rejuvenate damaged cells, allowing them to function normally again. This not only slows down the progression of fibrosis but also promotes the repair and regeneration of lung tissues.
 
Another advantage of this therapy is its potential to enhance the body’s natural ability to clear fibrotic tissue. Healthy fibroblasts and macrophages play a key role in breaking down excessive fibrous deposits in lung tissue. When these cells become senescent, their ability to perform this function declines. By reversing cellular senescence, Box A therapy restores this essential process, aiding in the gradual removal of scar tissue.
 
Implications for Future Treatments
These findings open the door for further research into using Box A gene therapy for human pulmonary fibrosis patients. The current treatment options for pulmonary fibrosis primarily involve antifibrotic drugs that slow disease progression but do not reverse lung damage. Box A therapy, however, provides a new avenue for not only stopping fibrosis but also potentially reversing it.
 
Further research and clinical trials will be necessary to determine how effective and safe Box A therapy is in human patients. If successful, this gene therapy could become a groundbreaking treatment not just for pulmonary fibrosis but also for other diseases associated with cellular senescence, including liver fibrosis and age-related degenerative conditions.
 
Challenges and Next Steps
Despite these promising results, there are several challenges that need to be addressed before Box A therapy can be used in clinical settings. One of the main concerns is the method of delivery. While the study successfully administered Box A using nanoparticles in rats, optimizing this method for human patients will require further refinement.
 
Another potential hurdle is understanding how Box A therapy interacts with different types of pulmonary fibrosis. Idiopathic pulmonary fibrosis, for example, has a more complex pathology compared to fibrosis caused by environmental factors or infections. Researchers will need to conduct additional studies to determine which patients are most likely to benefit from this treatment.
 
Furthermore, large-scale clinical trials will be required to assess the long-term effects and potential side effects of Box A therapy. Gene therapies are still a relatively new field in medicine, and ensuring the safety of this approach will be a top priority.
 
Conclusion
The discovery of Box A gene therapy as a potential treatment for pulmonary fibrosis represents a significant breakthrough in medical science. By targeting the root cause of fibrosis - cellular senescence - this innovative therapy offers hope for patients suffering from this debilitating disease.
 
The study findings were published in the peer-reviewed journal: BMC Pulmonary Medicine.
https://link.springer.com/article/10.1186/s12890-025-03522-2
 
As researchers continue to refine this approach and move towards clinical trials, the possibility of reversing pulmonary fibrosis may soon become a reality.
 
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