Gene Therapy Breathes New Hope into Cystic Fibrosis Treatment

Gene therapy is stepping into the spotlight as a promising avenue for treating cystic fibrosis (CF), a chronic genetic disorder that affects around 1,000 new individuals in the U.S. each year. The disease stems from mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, which encodes a protein responsible for regulating salt movement in and out of cells. These mutations disrupt salt balance, causing cells to become dehydrated and leading to the buildup of thick, sticky mucus in the lungs and other organs. This buildup hinders breathing and increases susceptibility to infections.

Until recently, treatment for CF has focused primarily on alleviating symptoms and enhancing quality of life. CFTR modulators, drugs that aim to improve the function of the faulty CFTR protein, have changed the treatment landscape for many—but not for all. Roughly 10% of CF patients cannot benefit from existing modulator therapies, making gene therapy a crucial next step.

Gene therapy targets the root cause by delivering a correct copy of the CFTR gene to affected cells, restoring their ability to produce the functioning CFTR protein. This approach is now gaining traction with several therapies in clinical trials.

One of the most significant developments came in February when Boehringer Ingelheim initiated clinical testing for BI 3720931, the first inhaled lentiviral gene therapy for CF. This therapy uses a modified lentivirus—derived from HIV—to deliver functional CFTR DNA to airway epithelial cells. Administered through a nebulizer, the misted solution reaches lung cells directly, potentially increasing its therapeutic impact.

BI 3720931 is being developed in collaboration with the UK’s Respiratory Gene Therapy Consortium (GTC) and Oxford Biomedica (OXB). The ongoing phase 1/2 LENTICLAIR 1 trial is designed to assess the therapy’s safety, tolerability, and efficacy in adults who are ineligible for CFTR modulator treatments. The trial’s first phase will test different dosing levels, while phase 2 will involve a randomized, double-blind, placebo-controlled design to evaluate clinical outcomes. A long-term follow-up study will also monitor participants beyond the initial treatment period.

“This is a crucial moment in the development of BI 3720931,” said Paola Casarosa of Boehringer Ingelheim. “We’re proud to advance this candidate in partnership with the GTC and OXB, reflecting years of shared commitment.”

Other companies are pursuing alternative gene therapy strategies as well. California-based 4D Molecular Therapeutics is developing 4D-710, a therapy that uses an adeno-associated virus (AAV) to deliver a functional CFTR gene via inhalation. The therapy is currently in a phase 1/2 trial focused on safety, tolerability, and determining optimal dosage, along with secondary measures like lung function and patient quality of life.

Spirovant Sciences is also advancing its AAV-based candidate, SP-101, which is unique for being combined with the chemotherapy agent doxorubicin to enhance gene transfer. In preclinical trials involving ferrets, this inhaled combination therapy successfully triggered CFTR protein expression. The first patient was dosed in a phase 1/2 trial in November, marking a major milestone for the program.

Meanwhile, Krystal Biotech is developing KB407, which utilizes a modified herpes simplex virus-1 (HSV-1) vector to carry two copies of the CFTR gene to lung cells. Drawing on the same platform behind its FDA-approved Vyjuvek gene therapy, KB407 is designed to deliver high genetic payloads without integrating into the host genome, potentially allowing repeat dosing.

ReCode Therapeutics is exploring a different angle altogether. Its investigational drug RCT2100 is an mRNA-based therapy aimed specifically at patients with nonsense mutations—those whose CFTR genes contain premature stop signals that halt protein production. Using lipid nanoparticles to deliver CFTR mRNA directly to lung cells, RCT2100 provides the correct protein-building instructions, bypassing the defective gene altogether. Now in phase 1b trials, the therapy has received Orphan Drug Designation from the FDA and has financial backing from the Cystic Fibrosis Foundation.

Despite the promise, gene therapy for cystic fibrosis has been slow to materialize. Since the CFTR gene was discovered in 1989, delivering functional versions to the lungs has posed major challenges. Over 2,000 variants of the CFTR mutation have been identified, complicating treatment strategies. Nonetheless, the field is finally gaining momentum, driven by advances in delivery systems and a growing need for options for the 10% of patients who remain untreated.

With multiple approaches in development, the CF community is entering a hopeful era where treatment may no longer just manage symptoms—but address the disease at its genetic core.

Source :https://www.labiotech.eu/in-depth/gene-therapy-cystic-fibrosis/

This is non-financial/medical advice and made using AI so could be wrong