Cystic fibrosis (CF) is a chronic genetic disease that affects more than 4,300 Canadians and tens of thousands worldwide (CF Canada, 2023). It’s caused by mutations in the CFTR gene, which encodes a protein responsible for regulating salt and water flow in and out of cells. When this protein is dysfunctional or missing, it leads to the accumulation of thick, sticky mucus, especially in the lungs and digestive tract, causing persistent infections, inflammation, and impaired nutrient absorption.

What’s Happening at the Molecular Level?

The CFTR protein functions as a chloride channel on the surface of epithelial cells. In healthy individuals, this channel helps maintain the thin mucus layers needed to protect and clear the lungs and intestines. In people with CF, defective CFTR means mucus becomes dehydrated and immobile, trapping bacteria and triggering chronic inflammation. Over time, this contributes to progressive lung damage and complications in other organs. Understanding this basic defect has been essential to developing therapies that go beyond symptom management to address the root cause of CF.

From Symptom Management to Targeted Therapies

Just a few decades ago, CF was managed almost entirely by treating symptoms, using antibiotics to control infections, chest physiotherapy to clear mucus, pancreatic enzyme supplements, and nutritional support. These treatments helped manage complications, but didn’t address the underlying cause of the disease.

That changed with the introduction of CFTR modulators,  drugs that directly target the defective CFTR protein. Rather than just treating the downstream effects, modulators aim to restore the protein’s function at the cellular level.

Different mutations in the CFTR gene lead to different defects in how the protein is made, trafficked, or functions. Modulators are grouped based on which part of this process they fix:

• Correctors (e.g., lumacaftor, tezacaftor, elexacaftor) help CFTR proteins that are misfolded inside the cell. Normally, these malformed proteins are destroyed before they can reach the cell surface. Correctors help them fold properly and move to the membrane, where they can function.

• Potentiators (e.g., ivacaftor) help CFTR proteins that reach the cell surface but can’t open effectively. They increase the opening (or “gating”) of the chloride channel, allowing chloride ions to flow more freely across the membrane.

• Stabilizers (currently in development) aim to keep the CFTR protein functioning longer once it reaches the membrane, preventing it from degrading too quickly.

Trikafta: Transforming Outcomes for Many

Trikafta is currently the most widely used CFTR modulator therapy, offering clinical benefits for approximately 90% of people with CF. It combines three drugs (elexacaftor, tezacaftor, and ivacaftor) that work together to correct multiple defects in the CFTR protein.

For eligible individuals, Trikafta has been shown to improve lung function, reduce pulmonary exacerbations, and enhance overall quality of life. While not a cure, Trikafta represents a major shift in CF care, helping many people breathe easier, stay out of the hospital, and live more independently.

What About the 10% Still Waiting?

Roughly 10% of people with CF have rare or non-responsive mutations that don’t benefit from current modulators. For this group, researchers are exploring next-generation treatments such as:

• Gene editing (e.g., CRISPR) to directly repair the faulty gene.

• mRNA-based therapies to deliver correct CFTR instructions to the cell.
  
  

These approaches are currently in clinical trials, and while early, they represent an important step toward inclusive, mutation-agnostic therapies.

Understanding the Ongoing Burden of CF

Even as new therapies redefine what it means to live with CF, the burden of disease remains real. Many patients still face:

• Intensive daily treatment regimens

• Recurrent infections, including from antibiotic-resistant bacteria

• Frequent hospitalizations and declining lung function over time

• Social, mental health, and financial challenges

Modulators have changed the CF landscape,  but not eliminated the disease. That's why understanding the full picture of CF, beyond just CFTR correction, remains a research priority.

What We’re Doing at the MHD Lab

At the Microbe-Host Dynamics (MHD) Lab at Dalhousie University, we study how CFTR dysfunction and modulator therapies influence the lung microbiome, immune system, and disease progression. Our research focuses on:

1. Population-level trends in CFTR modulator use across Canada

2. How pathogens (like Pseudomonas aeruginosa) respond to modulator therapy

3. How immune signaling and inflammation are impaired in CF

By combining clinical data, microbial ecology, and immunology, we aim to uncover how therapies affect not just mucus, but the broader host–microbe landscape in the lungs,  and what this means for long-term health outcomes.

We hope to use this translational science by taking real-world clinical questions and using lab-based research to help inform care, policy, and future treatments.

Helpful Resources & Support

If you or someone you know is living with CF, here are some trusted organizations that provide information, advocacy, and supports:

Cystic Fibrosis Canada – Advocacy, care guidelines, and research updates    

Cystic Fibrosis Foundation (US) – Comprehensive treatment info and clinical trial news 

CF and Mental health - Mental health resources for people living with CF  

CF Get Loud – Personal stories, community action, and awareness   

CFTR2 Mutation Database – Learn about your CFTR mutation and eligibility for therapies   

Written on June 18th, 2025