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NTU Singapore's Breakthrough Inhaled Therapy for Severe Lung Infections

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NTU Singapore Advances Respiratory Medicine with Innovative Inhaled Therapy

Nanyang Technological University (NTU) Singapore is at the forefront of medical innovation, particularly in addressing critical respiratory challenges. A recent breakthrough from NTU's Lee Kong Chian School of Medicine (LKCMedicine) introduces a promising inhaled treatment designed to mitigate lung damage from severe infections. This development underscores NTU's pivotal role in higher education and translational research, positioning Singapore as a hub for advanced biomedical solutions.

The therapy targets persistent inflammation that lingers even after pathogens like viruses or bacteria are cleared, a common issue in conditions such as pneumonia, influenza, and acute respiratory distress syndrome (ARDS). By focusing on university-led research, NTU not only contributes to global health but also trains the next generation of scientists and clinicians in Singapore's vibrant higher education landscape.

The Burden of Severe Lung Infections in Singapore

Singapore faces a significant respiratory health crisis, with pneumonia ranking as the second leading cause of death after cancer, accounting for around 20-23% of fatalities annually. Over 10,000 hospital admissions for pneumonia occur each year, straining healthcare resources and highlighting the urgency for new treatments. Nontuberculous mycobacterial (NTM) infections, particularly from drug-resistant Mycobacterium abscessus, are rising, now rivaling tuberculosis cases in incidence. NTU's research directly addresses these challenges, leveraging its expertise in Asian-centric studies through initiatives like the Academic Respiratory Initiative for Pulmonary Health (TARIPH).

In higher education, NTU's focus on lung health reflects Singapore's investment in university research, with TARIPH securing a landmark S$10 million National Medical Research Council grant in 2025—the first national funding for respiratory health.

How the Inhaled ANGPTL4 Therapy Works

The new therapy employs an antisense oligonucleotide (ASO) targeting Angiopoietin-like protein 4 (ANGPTL4), a protein upregulated during inflammatory stress. ANGPTL4—full form Angiopoietin-like 4—increases vascular permeability, leading to fluid leakage into lung air sacs (alveoli) and subsequent fibrosis or scarring. The inhaled delivery mimics asthma inhalers, ensuring high local concentrations in the lungs with minimal systemic exposure, thus reducing side effects.

This RNA-based approach precisely modulates ANGPTL4 to preserve the lung barrier, curb excessive immune responses, and prevent long-term damage without compromising pathogen clearance. Developed over nearly a decade, it represents a shift from broad immunosuppressants to targeted molecular interventions.

Preclinical Results Showcase Efficacy

In rigorous preclinical models jointly led by NTU and Southern University of Science and Technology (SUSTech), the therapy demonstrated compelling results. It significantly reduced inflammation and fluid accumulation in bacterial pneumonia and viral influenza models, while decreasing scarring in pulmonary fibrosis simulations. Breathing function improved markedly, validating its potential across acute infections and chronic conditions.

Early safety data confirmed the treatment's localization to the lungs, supporting higher dosing at the site of injury. These findings, detailed in Advanced Science (DOI: 10.1002/advs.202501909), pave the way for clinical advancement.

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Preclinical model showing reduced lung inflammation from NTU's inhaled therapy

Key Researchers Driving NTU's Innovation

Associate Professor Andrew Tan Nguan Soon, Vice-Dean (Innovation and Enterprise) and Provost’s Chair in Metabolic Disorders at LKCMedicine, co-led the study. His team, including PhD students Damien Chua and Joseph Kim, Research Associate Liu Yu Xuan, and Senior Research Fellow Cheng Hong Sheng, collaborated with Asst Prof Li Liang from SUSTech and Lipigon Pharmaceuticals AB. "This lays the foundation for RNA-based treatments for lung diseases," says Prof Tan.

In parallel, NTU's School of Biological Sciences (SBS), under Professor Gerhard Grüber, advanced a QcrB inhibitor (ND-011458) against M. abscessus via cryo-EM structures, published in Nature Communications (DOI: 10.1038/s41467-026-70805-5). These efforts highlight NTU's interdisciplinary strength in higher education.

TARIPH: NTU's National Platform for Lung Health

NTU's TARIPH Centre coordinates Singapore's lung research, uniting nine organizations including public healthcare clusters. The S$10M grant funds Asian-specific studies on asthma, COPD, and post-ICU care, establishing disease registries and trials. This platform exemplifies how Singapore universities drive public health advancements.

Advantages Over Traditional Treatments

  • Targeted Action: Unlike systemic corticosteroids, which have limited evidence for bacterial pneumonia, this therapy acts locally.
  • Safety: Minimal off-target effects, improving tolerability.
  • Versatility: Effective against viral/bacterial damage and fibrosis.
  • Patient-Friendly: Inhaled format enhances compliance.

Experts like Prof David Lye note its potential to boost survival in severe cases.

Path to Patients: Patents and Trials Ahead

A joint patent protects the platform, with non-human primate studies and IND preparation underway. Lipigon supports translation, signaling commercialization potential. NTU's innovation ecosystem accelerates this from bench to bedside.

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NTU researchers collaborating on lung therapy development

NTU's Broader Impact on Singapore Higher Education

NTU ranks among Asia's top universities, with LKCMed and SBS fostering medtech talent. Current openings include Research Assistants in respiratory cell culture, attracting global experts to Singapore.Explore NTU careers This positions graduates for roles in biotech, aligning with Singapore's life sciences push.

Future Outlook: Transforming Respiratory Care

NTU's therapies promise faster recovery, fewer complications, and personalized medicine for Singapore's aging population. As universities like NTU lead, expect more RNA innovations and collaborations, enhancing higher ed's societal role.

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Frequently Asked Questions

🫁What is NTU's new inhaled treatment for lung infections?

NTU Singapore's therapy uses ANGPTL4 antisense oligonucleotides delivered via inhalation to reduce inflammation and damage post-infection. Details here.

🔬How does ANGPTL4 contribute to lung damage?

ANGPTL4 increases vascular permeability during stress, causing fluid leakage and fibrosis. The therapy modulates it precisely.

📊What were the preclinical results?

Reduced inflammation, fluid, scarring in pneumonia, flu, fibrosis models; improved breathing. Published in Advanced Science.

👥Who leads this NTU research?

Assoc Prof Andrew Tan (LKCMed) and Asst Prof Li Liang (SUSTech), with NTU PhD students and Lipigon.

🇸🇬Why is pneumonia critical in Singapore?

2nd leading cause of death (~20%), >10k admissions/year. NTM rising.

⚖️How does it compare to corticosteroids?

More targeted, localized; better for bacterial cases where steroids lack evidence.

🏛️What is TARIPH at NTU?

NTU-led national platform with S$10M grant for Asian lung research.

🦠NTU's other lung innovation?

QcrB inhibitor ND-011458 for M. abscessus via cryo-EM (Nature Comm).

🚀Future steps for the therapy?

Non-human primate trials, IND filing; patent protected.

💼Career ops at NTU respiratory research?

RA/Associate roles in cell culture, fellowships; see NTU careers.

🧬How does NTU support RNA medicine?

Via innovation initiatives, positioning SG in emerging fields.