The Cystic Fibrosis Unit of Vall d'Hebron University Hospital and the Pneumology group of Vall d'Hebron Research Institute (VHIR) have initiated a pioneering phase I clinical trial to study a DNA corrective therapy for the treatment of cystic fibrosis. Recently, it has included the first patient in this international study, in which Vall d'Hebron is the only center in Spain to participate.

Cystic fibrosis is a genetic disease due to a mutation in the CFTR gene that causes the accumulation of thick, sticky mucus mainly in the lungs, but also in the digestive system and other organs. “With this treatment, we aim to introduce into the cell nucleus a functional copy of the CFTR gene to restore its activity and thus reduce the impact of this disease. These therapies will mark a breakthrough in our patients, correcting the genetic defect in the bud”, explains Dr. Antonio Álvarez, coordinator of the Adult Cystic Fibrosis Unit and principal investigator of the Pneumology group at VHIR.

In this first phase, the research will evaluate the safety and the optimal dose in order to evaluate its efficacy in a second phase. “We will see the results in the coming months to know if in a few years they can be applied in clinical practice. It is very significant that different genetic treatment approaches are already being used in patients, something that a few years ago was still seen as a long way off”, adds Dr. Alvarez.

Clinical trials with genetic treatments

The Cystic Fibrosis Unit of Vall d'Hebron is a leader, together with the most prestigious centers at international level, in the performance of clinical trials with the most advanced therapies, which seek solutions that bring us closer to curing the disease. As it is a genetic disease, these solutions consist of different approaches to possible genetic treatments.

The team is currently involved in several clinical trials with such therapies. In addition to the recently initiated clinical trial, there is also a study with antisense oligonucleotides, which aims to correct certain specific mutations, and one with messenger RNA therapy, which aims to restore the defective messenger RNA coding for the CFTR protein with the correct sequence so that the protein is synthesized normally.

Dr. Almudena Felipe, predoctoral researcher in the Pneumology group at VHIR, explains that "the ultimate goal, common to all of them, is to restore the synthesis of the CFTR protein and make it a functional protein". In addition, all these treatments share the same route of administration of the product, through nebulization. ‘’CFTR protein correction would only be performed at the pulmonary level, but considering that respiratory involvement is the majority of patients, we hope that this will lead to an improvement in survival and quality of life for patients”, says Dr. Felipe.

The collaboration of a multidisciplinary team and of patients

Being at the forefront of all these trials and others involves a great effort and commitment from the entire research team. "These are complex clinical trials, very strict and meticulous, which require the utmost dedication", emphasize Ares Demoner and Sonia López, coordinators of the studies in the Pneumology group at VHIR. "The role of nursing is essential, as these patients are subjected to many controls, examinations and analytical tests in order to evaluate the safety of treatment objectively", says Laia Verdejo, nurse at the Cystic Fibrosis Unit and the Pneumology group at VHIR.

In addition, the collaboration of patients is essential, as well as the help provided by patient associations, such as the Catalan Cystic Fibrosis Association. "The symbiosis between patient associations and healthcare staff and working together with the same objective is essential to improve the quality of life and survival of people with cystic fibrosis", explains Dr. Álvarez.

The Cystic Fibrosis Unit: a benchmark in care and research

The Cystic Fibrosis Unit at Vall d'Hebron University Hospital started in 1994 and currently manages more than 500 patients, including adults and children, which makes it the largest Cystic Fibrosis Unit in Spain and one of the largest on the international scene with extensive experience in the management of these patients as well as in research into this pathology. In 2018, thanks to the support of the Daniel Bravo Foundation and the Catalan Cystic Fibrosis Association, a comprehensive renovation and expansion of the entire Unit was carried out, following European standards and adapting to the current needs of the disease.

The Unit has been recognised by the Spanish Cystic Fibrosis Society as a Reference Unit of Excellence and is the only Spanish center specializing in cystic fibrosis to form part of the European Reference Network on Respiratory Diseases (ERN Lung - CF). It has also received accreditation and has been a member of the European Clinical Trial Network - European Cystic Fibrosis Society (CTN - ECFS) for more than 14 years, which has allowed it to be always active in the latest studies being carried out, as was the case with the development of CFTR modulators that are currently already in use in clinical practice and have radically changed the outlook and survival of people with cystic fibrosis.