Discovery of Corrector Drugs' Is Key to Effective Treatment of Cystic Fibrosis, RCSI Research

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Discovery of ‘corrector drugs' is key to effective treatment of Cystic Fibrosis, RCSI Research Day hears

12/03/2015 20:58:00

Discovery of new corrector drugs that target the genetic mutation which is the underlying cause of cystic fibrosis, rather than the symptoms, is key to developing effective treatments for the condition, an expert in cystic fibrosis drug discovery has said. Research into these targeted treatments is the topic of a keynote address by Professor Luis Galietta, Professor in Molecular Genetics at the University of Genova, who will deliver the John J Ryan Distinguished Lecture at RCSI Research Day 2015, which is taking place at the Royal College of Surgeons in Ireland (RCSI) today.

CF is caused by mutations that abolish the function of CFTR, a protein that is needed to transport chloride and bicarbonate across cell membranes. CF mutations have been grouped in classes according to the mechanism through which they affect this protein. 10% of all CF patients with class 3 mutations can benefit from a recently approved drug, Kalydeco, which has shown to be highly effective. However, the majority of CF patients (70-90%) have different mutation (F508del) and require a different type of pharmacological treatment.
In his talk entitled "Pharmacological correction of the cystic fibrosis basic defect: problems and opportunities", Professor Luis Galietta will describe how present scientific research efforts are directed towards the identification of drugs, known as correctors, which can lessen the effects of F508del mutation. Professor Galietta and his team are among those who have been researching effective correctors by various strategies, including screenings on cultured cells of large collections of chemical compounds looking for molecules that improve the stability and function of mutant CFTR protein.
Cystic fibrosis (CF), one of the most frequent genetic diseases, is characterised by a progressive and irreversible damage of lungs, pancreas, and other organs. Ireland has the highest proportion of CF people in the world with approximately 1,200 patients suffering from this inherited chronic disease. (Source: Cystic Fibrosis Ireland)
RCSI's annual Research Day provides scientists with the opportunity to showcase their most recent research findings. The latest advances in biomedical sciences, clinical research, population health sciences, healthcare delivery and health professions education are just some of the topics featured in studies which will be presented today to more than 300 researchers who are expected to attend.
Professor Ray Stallings, Director of Research at RCSI said: ‘RCSI is committed to supporting and nurturing an active research community and the annual Research Day is a vital platform for highlighting the scope of research taking place across the different disciplines in the College. As one of Ireland's premier research institutions, exposure to world-class research begins at undergraduate level right up to the highest-calibre research-active academic staff, enabling us to train new generations of researchers and clinician scientists. We are delighted to welcome Professor Luis Galietta to share his renowned expertise in cystic fibrosis drug discovery to present his ground-breaking research with us.'

The emphasis for RCSI Research Day is on research presentations by investigators early in their career, post-doctoral fellows, post-graduate and undergraduate scholars and academic staff. All oral presentations and poster presentations will be judged and awards will be presented at a ceremony later this evening.

Additional research presented at the RCSI Research Day:

RCSI team discover new tissue regeneration method to enhance tissue repair and block disease-causing genes

Osteoarthritis and diabetes among conditions that may benefit from regenerative therapies

Researchers from the Tissue Engineering Research Group (TERG), RCSI Department of Anatomy have developed a unique therapeutic platform that potentially can be used to block harmful genes and enhance beneficial ones and thus has potential to repair damaged or diseased organs for a myriad of conditions, it was reported today at the RCSI Research Day 2015, which is taking place at the Royal College of Surgeons in Ireland (RCSI).
The discovery will potentially lead to new treatment for diseases that would benefit from tissue repair, including repair of cartilage in osteoarthritis and vascular tissue in diabetes. In addition to enhancing tissue repair by ‘switching on' beneficial genes, the therapeutic platform has the ability to ‘switch off' genes that cause disease, such as genes that cause excessive bone growth in osteoarthritis, which is a major new finding that has emerged from the study.
Professor Fergal O'Brien, Head of the Tissue Engineering Research Group at RCSI and lead-Principle Investigator on the project said ‘The platform biomaterials developed in this study have potential for the regeneration of numerous degenerated or diseased tissues in the body when combined with different therapeutic microRNA activators or inhibitors. The obvious application of this technology is bone repair but we also have particular interest in using the platform to deliver microRNAs that improve the regeneration of tissues which suffer from a compromised blood supply- for example in diabetic patients'.
The system allows for the local delivery of both activators and inhibitors of micro-ribonucleic acids (microRNAs), an RNA interference technology alternative to gene therapy, in combination with nanoparticles and a collagen-based scaffold biomaterial, designed specifically for tissue repair. In this study, the team developed a highly efficient microRNA delivery approach by implementing their own in-house scaffold-based transfection system, which involved the combination of a collagen-based scaffold previously developed for tissue repair and optimised nano-hydroxyapatite particles, previously developed for plasmid DNA gene delivery, as safe and effective non-viral microRNA delivery vectors for human stem cells.
The research was the result of a multi-disciplinary effort between cell biologists, clinicians and engineers in the TERG, which is part of the Advanced Materials and Bioengineering Research (AMBER) Centre, and was led by Prof. Fergal O'Brien and Dr. Garry Duffy in RCSI. Results of this study have just been published in the leading specialist journal in the field, Journal of Controlled Release, with Irene Mencía Castaño, a PhD student in the TERG supervised by Prof. O'Brien, Dr. Duffy and Dr Caroline Curtin, as first author. This work was supported by the BioAT PhD Structured Programme funding bodies PRTL (Programme for Research in Third Level Institutions) Cycle 5 as well as through the European Research Council.
The relevance of the innovative microRNA-scaffold platforms described within this study is highlighted by the magnitude of funding being invested recently in RNA-based biotechnological companies. In addition, Prof. O'Brien recently received a prestigious ‘Proof of Concept' grant from the European Research Council (ERC), an award only available to researchers that have already been awarded an ERC Investigator grant. This award will allow further research on the platform with particular focus on cartilage repair.
RCSI is among the top 50 most international universities in the world (Times Higher Education University World Rankings, 2014-15). It is a not-for-profit health sciences institute focused on education and research to drive positive change in all areas of human health worldwide. RCSI is headquartered in Dublin and is a recognised College of the National University of Ireland. In 2010, RCSI was granted independent degree awarding status by the State, which enables the College to award degrees alongside its traditional powers to award licentiates.

For further information on RCSI Research Day 2015 visit: