In the UK and Europe, they are testing inhaled gene therapy aimed at treating cystic fibrosis.

Cystic fibrosis (CF) is caused by defects in the CFTR gene, leading to the accumulation of thick, sticky mucus in the lungs and digestive system. This results in lung infections and gradually impairs the ability to breathe. A new gene therapy utilizing a lentiviral vector works by inserting a functioning copy of the CFTR gene into the DNA of the epithelial cells in the patient's airways.

Currently, some individuals with CF respond well to relatively new treatment methods known as CFTR modulators, which target the CFTR-related protein. However, approximately 10-15% of patients do not benefit from these medications.

The aim of the new investigational drug, known as BI 3720931, is to enhance lung function and reduce the frequency of exacerbations (flare-ups of the disease that often lead to hospitalization) in individuals with CF, regardless of the type of mutation, including those who are genetically unable to benefit from other CF treatment methods.

The LENTICLAIR 1 trial, which will assess the safety, tolerability, and effectiveness of the treatment, is being conducted by the biopharmaceutical company Boehringer Ingelheim in partnership with the UK Cystic Fibrosis Gene Therapy Consortium (GTC) and OXB (formerly Oxford Biomedica). Approximately 36 men and women with cystic fibrosis will receive treatment at centers in the UK, France, Italy, the Netherlands, and Spain.

Cystic fibrosis is an inherited, incurable disease that worsens over time. It is estimated that 105,000 people worldwide are affected. There are over 2,000 known mutations in the CFTR gene, which lead to varying degrees of disease severity.

Lentiviral vectors are a type of gene therapy that utilize the ability of lentiviruses to infect human cells. Lentiviruses are a family of viruses that infect a host by integrating their genetic material into the host cell's genome. By modifying lentiviruses, scientists have been able to use them as a means to insert beneficial genes into cells.

The research is led by Eric Alton, a professor of gene therapy and respiratory medicine at the National Heart and Lung Institute. He coordinates the UK CF Gene Therapy Consortium, which unites three centers in the UK (the University of Edinburgh, the University of Oxford, and Imperial College London) focusing on translational gene therapy for respiratory diseases. He is also an honorary consultant physician at Royal Brompton Hospital, one of the UK's research centers.

“The UK Cystic Fibrosis Gene Therapy Consortium is very pleased to reach this milestone after 24 years of dedicated efforts and close collaboration with our funding partners. While the immediate goal is to help patients who cannot use CFTR modulators, this new therapy has the potential to achieve long-lasting improvement in CFTR function and modify the disease in individuals with CF regardless of mutation type and, importantly, has the potential for re-administration if necessary.”

Eric Alton, Professor of Gene Therapy and Respiratory Medicine at the National Heart and Lung Institute.

Research scientists share that it has been incredibly rewarding to witness the health benefits provided by CFTR modulators, but it is disheartening that those who cannot access these medications urgently need alternative treatment options.

In this trial, they have opened new horizons by developing gene therapy capable of providing sustained CFTR expression. Scientists expressed gratitude to individuals living with CF who are willing to dedicate their time to trials of new drugs, without whom researchers could not achieve such progress.

In the first phase of the study, various doses of the drug will be administered to assess safety, tolerability, and dose selection for the second phase. In the second phase, two selected doses or placebo will be administered in a randomized, double-blind, placebo-controlled dose-escalation study to evaluate clinical efficacy and safety.

After the completion of the 24-week study period, participants will engage in long-term follow-up in the LENTICLAIR-ON study.