New Treatment for Cystic Fibrosis: Inhalable Gene Therapy

New Treatment for Cystic Fibrosis: Inhalable Gene Therapy

March 12, 2025 Catherine Williams - Chief Editor Health

Inhalable Gene Therapy Shows Promise for Cystic Fibrosis

Table of Contents

A collaborative effort involving nine European hospitals, including UMC Utrecht, is currently testing an innovative gene therapy for cystic fibrosis (CF). This new approach involves an inhalable treatment,marking the first time this method has been applied to combatting CF. The Lenticlair study is evaluating this treatment on individuals for whom existing medications have proven ineffective.

Cystic fibrosis, a rare genetic disorder, remains incurable. Approximately 25 babies are born with CF in the Netherlands each year. These patients have a defect in the CFTR gene, which is essential for producing a vital protein. A properly functioning CFTR gene ensures the protein effectively keeps mucus thin. Though, mutations in this gene lead to malformed or absent proteins, causing the mucus of CF patients to become thick and sticky.This results in complications in various organs, with the most severe effects occurring in the lungs. Breathing becomes challenging, worsening with age.Sadly, most CF patients do not live beyond the age of fifty.

Gene Therapy: A New Frontier for Cystic Fibrosis Treatment

Existing treatments, such as CFTR modulators, are effective for 85 to 90 percent of CF patients. These medications, available in pill or powder form, repair the misshapen proteins caused by the genetic defect. Though, a small subset of patients does not respond to these treatments as they produce no CFTR protein at all. According to Dr. Danya Muilwijk,a pulmonologist at UMC Utrecht involved in the gene therapy study,”They only recieve medication to combat their symptoms,such as inhaled antibiotics for infections and agents to help loosen the mucus.”

Dr. Muilwijk describes the first human study of this treatment as “groundbreaking.” For over three decades, scientists have been working on a drug that directly addresses the genetic defect in this patient group. their efforts have led to an innovative solution: an inhalable gene therapy.”With gene therapy, you introduce healthy genes into diseased cells, allowing the healthy genes to take over and produce good CFTR protein,” explains Dr. Muilwijk. “It is a therapy that is inhaled via a mask, so that the ‘good’ genes end up in the cells in the airways, which are often the most affected in CF.”

The Role of Viruses as Gene Carriers

Typically, the body’s immune system prevents foreign particles, such as pathogens, from infiltrating cells. However, gene therapy requires this infiltration. A carrier is needed to transport the gene into the cell. “In this therapy, we use a harmless lentivirus for this purpose,” says Dr. Muilwijk. “That virus can transfer the CFTR genes, but it does not make you sick.” Once the genes reach the airway cells and take over the function of the diseased genes, the effect is intended to be long-lasting. dr. Muilwijk notes, “we expect that patients will only need a few doses of this drug in their lifetime.”

The discovery of the CFTR gene in the 1990s identified CF as a prime candidate for gene therapy.It is a monogenetic disease, meaning only one gene needs to be repaired.

Though, developing a treatment that doesn’t trigger an overwhelming immune response has been challenging. The carrier must deliver the genes specifically to the correct organs and cells. “If you administer this treatment via the bloodstream, it is largely filtered out by the liver,” explains Dr. Muilwijk. “Then it does not reach the lungs.” The Lenticlair study addresses this issue by using nebulization, delivering the drug directly to the airway cells through a mist.

“with this treatment, we are taking a huge step, because for CF patients, their lung problems are the most debilitating. That is also what they ultimately die from,” says Dr. Muilwijk.”But there is still more work to be done to find a treatment that also reaches the other organs, as is the case with CFTR modulators.”

Safety and Side Effects of Gene Therapy

The clinical study focuses on patients who need the treatment most: those who produce no CFTR protein. However, Dr. Muilwijk believes that gene therapy could possibly benefit all CF patients in the future. “There are many different mutations that can cause a defect in the CFTR gene.But with this gene therapy, which delivers a very healthy gene, in theory, all patients can be helped in the future.”

According to Dr. Muilwijk,it will take at least two to ten years before the drug is available on the market. The initial phase focuses on testing safety and side effects,not on determining the treatment’s effectiveness. “Explaining that well to people who are considering participating in the study is a delicate process,” says the pulmonologist. “It is possible that the patient will benefit from participation, but that is not the goal of the study in this phase, and we cannot guarantee that.”





Inhalable Gene Therapy Shows Promise for Cystic Fibrosis: Your Questions answered

This article delves into the groundbreaking Lenticlair study, an inhalable gene therapy showing promise for treating cystic fibrosis (CF).We’ll explore the science behind this therapy, its potential benefits, and what the future holds for CF patients.

What is Cystic Fibrosis (CF)?

Cystic fibrosis is a rare, inherited genetic disorder that primarily affects the lungs but can also impact other organs. A defective CFTR (cystic fibrosis transmembrane conductance regulator) gene causes the disease.

Approximately 25 babies are born with CF in the Netherlands each year.

People with CF experience a buildup of thick, sticky mucus in the lungs, leading to breathing difficulties and increased susceptibility to infections.

The median life expectancy for CF patients is currently around 50 years.

How Does the CFTR Gene Affect Cystic Fibrosis?

the CFTR gene provides instructions for making a protein that controls the movement of salt and water in and out of cells. A properly functioning CFTR protein keeps mucus thin and free-flowing. When the CFTR gene is mutated, it can result in either malformed or absent CFTR proteins. This causes the mucus to become thick and sticky,leading to various complications,particularly in the lungs.

What are Current Treatments for Cystic fibrosis?

Existing treatments for CF focus on managing symptoms and improving quality of life. These include:

CFTR Modulators: These medications,available as pills or powders,help repair misshapen CFTR proteins caused by genetic defects. These treatments are effective for 85-90% of CF patients.

Medications to Combat Symptoms: For patients who don’t respond to CFTR modulators, treatments include inhaled antibiotics for infections and agents to loosen mucus.

What is Gene therapy for Cystic Fibrosis?

Gene therapy aims to correct the underlying genetic defect in CF by introducing a healthy CFTR gene into the patient’s cells.

Dr. danya Muilwijk, a pulmonologist at UMC Utrecht, describes the current study as groundbreaking, representing over three decades of research.

The goal of gene therapy is for the healthy gene to take over and produce functional CFTR protein.

How Does Inhalable Gene Therapy Work?

The Lenticlair study uses an inhalable gene therapy administered via a mask.

The “good” genes are delivered directly to the cells in the airways, which are most affected by CF.

The therapy uses nebulization, delivering the drug directly to the airway cells through a mist, bypassing filtration by other organs like the liver.

What Role Do Viruses Play in Gene Therapy?

Viruses are used as carriers to deliver the healthy CFTR gene into the cells.

The Lenticlair study uses a harmless lentivirus that can transfer the CFTR gene without causing illness.

The expectation is that a few doses of this gene therapy will have a long-lasting effect.

Why is CF a Good Candidate for Gene Therapy?

CF is a monogenetic disease, meaning it is caused by a defect in a single gene (CFTR). this makes it a prime candidate for gene therapy because only one gene needs to be repaired.

What are the Challenges of Developing Gene Therapy for CF?

developing effective gene therapy for CF has been challenging due to:

Immune Response: Avoiding triggering an overwhelming immune response is crucial.

Targeted Delivery: Ensuring the carrier delivers the gene specifically to the correct organs and cells (in this case, the lungs).

Reaching All Affected Organs: Current inhalable gene therapy primarily targets lung issues, but CF can affect other organs.

What are the potential Benefits of Gene Therapy for CF?

Gene therapy offers the potential to:

Address the root cause of CF by correcting the genetic defect.

improve lung function and reduce the frequency of lung infections.

* Potentially benefit all CF patients, irrespective of the specific CFTR mutation. This is particularly crucial for the 10-15% of patients who do not produce any CFTR protein and, therefore, do not respond to CFTR modulator drugs.

What are the Risks and Side Effects of Gene Therapy?

The initial phase of the Lenticlair study focuses on testing the safety and potential side effects of the gene therapy.While there is a possibility a patient might benefit from participation, it is not guaranteed.

When will Inhalable Gene Therapy for CF Be Available?

Dr. Muilwijk estimates that it will take at least two to ten years before the drug is available on the market.

Key Differences Between Current Treatments and Gene Therapy

| Feature | Current Treatments (e.g., CFTR Modulators) | Gene Therapy (Lenticlair study) |

| ——————- | —————————————— | ——————————————————————- |

| Mechanism | Repairs misshapen CFTR proteins | Introduces a healthy CFTR gene into cells |

| Target Patients | Effective for 85-90% of CF patients | Initially targeting patients who don’t respond to CFTR modulators |

| Delivery Method | Pills or powders | inhalable via a mask |

| frequency of Dose | Daily | Potentially a few doses in a lifetime |

| Focus | Managing symptoms and improving protein function | Correcting the underlying genetic defect |

Where is the Lenticlair Study Being Conducted?

The Lenticlair study is a collaborative effort involving nine European hospitals, including UMC Utrecht in the Netherlands.