FFC06/2024 Development of phage therapy for treating Mycobacterium abscessus lung infections in people with cystic fibrosis finaced for 75.450 Euros.
Mycobacterium abscessus (Mab) is an intrinsically drug resistant harmful bacterium which causes lung infections in people with cystic fibrosis (CF), making it very difficult to eliminate.
Bacteriophages are naturally occurring viruses capable of attacking bacteria and harmless to humans, which is why they could be used to treat people with infections by means of personalised therapies, i.e. specific to the type and variant of bacterium in question. Compared to the traditional antibiotic therapy, the use of bacteriophages would bring several advantages, such as greater efficacy, the absence of adverse effects on humans, and the possibility of replacement in case of the development of resistance in the bacterium.
The researchers will optimise and scientifically validate a collection of bacteriophages already developed in the lab, from which they will select the most effective ones capable of killing Mycobacterium abscessus. Moreover, they will genetically modify phages to make them more efficient and we test their effect in combination with antibiotics. Patient’s immune response to phages will also be tested.
The aim of the project is to provide more evidence about the efficacy of phage therapy for lung infections caused by drug-resistant mycobacteria such as Mab in people with CF and to define a specific protocol for treatment, which will be used for a future broader pilot study. The ultimate aim will be to provide treatment with bacteriophages in compassionate use to people with CF and Mycobacterium abscessus lung infection.
Responsabile: Mariagrazia Di Luca (Dipartimento di Biologia, Università degli Studi di Pisa)
Partner: Laura Rindi (Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Università degli Studi di Pisa); Andrea Moscatelli (Intensive Care Unit, Istituto “G. Gaslini”, Genova)
In the future, this study may pave the way to the use of bacteriophages to treat lung infections caused by other bacteria harmful to people with CF.

Kaftrio in the real life finaced for 40.000 Euros.
After the first project funded by the FFC Ricerca aimed to assess effectiveness and the safety of Kaftrio in patients with cystic fibrosis (pwCF) and advanced respiratory disease, that ends in the second half of 2023, a new multicentric study starts. This second observational, retrospective and prospective study, will be aimed to continue the assessment of effectiveness and safety in pwCF with advanced respiratory disease for overall 4 years (group A) and to enroll pwCF, in which Kaftrio has been supplied by the Italian Healthcare Service after July 2021 (group B). Real-world data will be obtained in patients of both groups, who will be 12 years of age or older and compound heterozygous for F508del and one minimal function mutation. Different effectiveness (lung function, body mass index, quality of life, sweat chloride) and safety (treatment-related adverse effects, interruption of the drug administration, increase in blood levels of hepatic enzymes and creatine phosphokinase) measurements will be evaluated for 2 years prior to and 2 or 4 years after Kaftrio was initiated. 
A secondary focus of the study will be directed toward pwCF who failed to obtain any beneficial improvement of lung function following treatment with Kaftrio (no responders). Considering different clinical characteristics and positive effects of the drug, these no responders will be compared to patients, which obtained a good increase in lung function (responders). Two sub-studies will be planned to compare the two groups for some relevant aspects of the responsiveness to the drug. The first sub-study will be mainly aimed to verify the correlation between ex vivo functional data of CFTR activity, obtained in nasal epithelia generated in vitro from responders and no responders, and their clinical response to the treatment with Kaftrio. The second sub-study will be mainly aimed to identify specific bacterial phenotypic and genetic characteristics of Pseudomonas aeruginosa, as markers of clinical response to treatment with the triple drug combination.
Project Manager: Cesare Braggion (Direzione Scientifica, Area Ricerca Clinica FFC Ricerca)
Partner: Maria Cristina Lucanto (Centro Regionale di Riferimento per la Fibrosi Cistica di Messina) Co-responsible Patner: 1) Nicoletta Pedemonte, UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, Genova; 2) Cristina Cigana, Unità di Infezioni e Fibrosi Cistica, Divisione di Immunologia, Trapianti e Malattie Infettive, Ospedale San Raffaele, Milano

Molecole 3.0 for cystic fibrosis financed for 100.000 Euros.
This project aims to develop a new class of modulators also active on rare CFTR mutations. The research group plans to synthesize and test the compounds following an iterative process of chemical synthesis and in-vitro functional evaluations to select and to optimize a small number of compounds. The project is based on the complementarity of the laboratories of Prof. Barraja and Dr. Galietta. The research groups share their expertise in synthetic organic chemistry and pharmacology and they use consolidated procedures of chemical synthesis.
Thanks to previous funded projects by FFC Ricerca, FFC#4/2018 and FFC#3/2020, researchers have identified a molecule, belonging to a new class of correctors. After the optimizations of this first obtained molecule, a new one, called PP028, was also generated. This molecule, was already tested on primary cells obtained from CF patients, showing a strong activity, especially when combined with known correctors.
The “Molecole 3.0” project aims to further improve the properties of this new class of correctors, through the coordinated work of pharmaceutical chemists who will generate new derivatives and by biologists who will evaluate the effectiveness of the compounds with in-vitro assays.
The synthesis process and the functional evaluations will allow to improve the potency and efficacy of the selected compounds. The functional tests will be conducted with in vitro tests, also using the Primary Culture Service (Servizio Colture Primarie) by FFC Ricerca. The optimization of the molecules will also take into account the properties of solubility, metabolic stability and the absence of toxicity, which are essential for any drug development. The ultimate goal of the project is to select a compound that can be considered for preclinical and clinical development.
Project manager: Paola Barraja (STEBICEF – Laboratorio di sintesi degli eterocicli, Università di Palermo) – Luis Galietta (Università degli Studi di Napoli Federico II e Telethon Institute of Genetics and Medicine – TIGEM, Napoli)

TASK FORCE FOR CYSTIC FIBROSIS (TFCF) finaced for 130.000 Euros.
Project Manager; Tiziano Bandiera (Dip. Drug Discovery and Development, Istituto Italiano Tecnologia, IIT, Genova);
Partner: Nicoletta Pedemonte (Lab. Genetica Molecolare, Istituto G. Gaslini, Genova);
Co-responsible Partner: Luis Galietta (Università degli Studi di Napoli Federico II e Telethon Institute of Genetics and Medicine – TIGEM, Napoli)