Funded Research

On this page:

• Conquer CF (GI) Innovation Grant 2021
• Abbie Fennessy Memorial Fellowship 2021
• CFWA Top Up Scholarship 2021
• CFWA - Golf Committee Contribution to CF Research 2021
• Special CF Research Seeding Grant 2021
• Lung Health Grant 2021 
• Innovation Grant 2021 
• Innovation Grant (sponsored by CFSA) 2021
• Conquer CF (Respiratory) Innovation Grant 2020
• CFWA Top UP Scholarships 2020
• Ann Maree Bosch Fellowship 2020
• Conquer CF (GI) Innovation Grant 2020
• Abbie Fennessy Memorial Fellowship 2020
• ACFRT Top-up Scholarship 2020
• David Millar Giles Innovation Grant (Extension) 2020
• Innovation Grant 2020
• Avatar acceptability: Views from the Australian Cystic Fibrosis community on the use of personalised organoid technology to guide treatment decisions 
• Antibiotics Special Issue: Challenges and Opportunities in Antibiotic Discovery and Development 
• Discovery of Cephalosporin-3′-Diazeniumdiolates That Show Dual Antibacterial and Antibiofilm Effects against Pseudomonas aeruginosa Clinical Cystic Fibrosis Isolates and Efficacy in a Murine Respiratory Infection Model 
• Ann Maree Bosch Career Fellowship 2019
• Antimicrobial Resistance in Cystic Fibrosis 2019 >
• David Millar Giles Innovation Grant 2019
• Innovation Grant 2019
• Innovation Grant 2019 (sponsored by CFCC Victoria)
• ACFRT Top Up Scholarships 2019
• WA Top Up Grants 2019
• Abbie Fennessy Memorial Fellowship 2019 (supported by Technipro-Pulmomed Pty Ltd & Cystic Fibrosis Australia (CFA))
• Special Fellowship Grant 2019 (CFCC Victoria)
• Innovation Grant 2018
• Ann Maree Bosch Career Fellowship 2018
• ACFRT Top Up Scholarships 2018
• Abbie Fennessy Memorial Fellowship 2018 (supported by Technipro-Pulmomed Pty Ltd & Cystic Fibrosis Australia (CFA))
• ACFRT in conjunction with CFSA Special Grant 2018
• Antimicrobial Resistance in Cystic Fibrosis 2018
• Innovation Grant in Partnership with CF Research Ltd (QLD) 2017
• Innovation Grant 2017
• Ann Maree Bosch Career Fellowship 2017
• WA Top Up Grants 2017
• ACFRT Top Up Scholarships 2017
• Abbie Fennessy Memorial Fellowship 2017 (supported by Technipro-Pulmomed Pty Ltd & Cystic Fibrosis Australia (CFA))
• Special Grants 2016

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David Millar Giles Innovation Grant 2019

Project Title:  An Australian Alliance of personalised lab grown mini-organs to save the rarest of them all

Name: Shafagh Waters

Institution: University of New South Wales

Value: $45,000

Duration: 1 Year

Summary: Some individuals with rare CFTR mutations have been shown to benefit from the available modulator therapies. Sadly, most will have no opportunity to access these breakthrough treatments. Currently no clinical test exists to predict patient’s response to a modulator drug. We are using a new technology in the field of personalised medicine. Stem cell derived mini-organs are generated from small biopsies serving as a personal CF model or an AVATAR. They are tested in the lab to predict an individual CF patients’ responses to therapeutic agents. Should one or more therapies prove effective in the lab, these can be recommended for use as targeted therapies for the patient.

In the last 2 years we have created AVATARs from children with CF that visit the Sydney Children’s Hospital and have predicted outcome of modulator therapies. In this application we propose to extend our platform to create an Australian-wide alliance for people with rare CF by extending to 11 CF clinics (6 paediatric and 5 adult). This project will provide a novel therapeutic opportunity, ultimately enabling ‘managed’ off-label access to the CFTR modulator therapies for individuals with rare CFTR mutations who show response to the therapy in a prospective mini-organ test.

Reports: Final Report

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Innovation Grant 2019

Project Title: Optimising patient-derived stem cell technology in cystic fibrosis to predict CFTR modulator response

Name: Gerard Kaiko

Institution: University of Newcastle and Hunter Medical Research Institute (Newcastle and Northern NSW)

Value: $80,000

Duration: 1 Year

Summary: CFTR modulator therapy offers great hope to improve the quality of life of cystic fibrosis (CF) patients with an array of different mutations. However, the high-cost, limitations of efficacy, and restrictions of therapies to clinical trial targeted mutations has created a powerful need for a lab test to better predict which CFTR mutations and which individual patients will respond to a given therapy. This type of precision-medicine is already critical but will only become more vital in the future as CFTR modulator therapy options increase. Stem cell technology has enabled patient cells to be readily grown in the laboratory. The use of ‘mini-guts’, grown from a CF patient intestinal biopsy, is being used in the Netherlands to suggest whether a given CFTR mutation may respond to a given therapy. To enable this type of testing to be put into practice in Australia there are two major questions that we aim to address in this project. Firstly, what is the optimal stem cell technology and functional test to apply to patient cells to determine whether they will respond to therapy. Secondly, can we predict a patient’s response to CFTR therapy in the clinic by testing the drugs on their stem cells.

Reports: 6 month report

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ACFRT Top-up Scholarship 2019

Project Title: Adverse Early Risk Factors for Adult Cardiovascular Disease in Paediatric Cystic Fibrosis

Name: Thomas Saunders

Institution: Murdoch Children's Research Institute

Duration: 3 years

Value: $5,000

Summary: Life with cystic fibrosis (CF) has undergone dramatic changes over the past decades, thanks to early interventions throughout childhood, including a high fat diet. Unlike previous generations, current CF children are living beyond their twenties, and now into their fifth or sixth decades. However the new medical challenges they will face are largely unknown. In particular, the impact of the leading causes of death worldwide, atherosclerosis and cardiovascular disease (CVD- heart attack and stroke), are unknown. Lung diseases similar to CF have much higher risks of CVD than the general population and there are increasing case reports of CF individuals developing CVD.

Atherosclerosis (hardening of the arteries) is thought to be largely preventable, especially when intervention starts in childhood. Risk factors such as inflammation, metabolic stress, and abnormal fat metabolism are all found in people with CF; but they are also prescribed high-fat diets, necessary to maintain good weight gain and growth. As CF life expectancy improves, and there are more and more instances of CVD in CF adults, novel studies aiming to detect it will be crucial.

This study investigates if CF children have early changes to blood vessels, biomarkers and immune system that may lead to atherosclerosis and CVD in adulthood. We will perform non-invasive ultrasounds looking at arteries, assess smaller vessels with retinal photographs, and measure specific biomarkers and immune cells in the blood.

This study is expected to show that CF children do have changes that suggest they may be at higher risk of atherosclerosis and CVD in the future. This will indicate if our current nutritional goals are sufficient, and guide changes to minimise the impact of CVD in CF adults. As people with CF live longer, it is critical that their increased survival also has improved quality of life with any treatment side-effects minimised. As such, this study will have a direct impact on how we treat people with CF in the future.

Reports:  None due

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ACFRT Top-up Scholarship 2019

Project Title: Computer Modelling of the Root Cause of Cystic Fibrosis

Name: Miro Astore

Institution: The University of Sydney

Duration: 3 years

Value: $5,000

Summary: We will use physics based atomic models to develop our understanding of cystic fibrosis and find treatments for it. With a focus on those who cannot currently access existing treatments.

Reports:  None due

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Abbie Fennessy Memorial Fellowship 2019

 (supported by Technipro-Pulmomed Pty Ltd & Cystic Fibrosis Australia)

Project Title: Infection Control and prevention with non-invasive ventilation use

Name: Olivia McGuiness

Institution: Royal Prince Alfred Hospital

Value: $5,000

Duration: 1 year

Summary: Infection control and prevention is of paramount importance in the health care setting. The National Health and Medical Research Council in collaboration with the Australian Commission on Safety and Quality in Healthcare emphasize the importance of standard and transmission-based precautions (NHMRC, 2010). Recommendations for infection control and prevention are outlined for several commonly used medical devices including central venous catheters and mechanical ventilators used in the intensive care. There are no such guidelines for non-invasive ventilator (NIV) devices. Due to its high costs, patients usually obtain these devices from a hospital or government equipment loan program. NIV devices are used or the management of patients with acute and chronic respiratory failure including those with chronic obstructive lung disease (COPD), sleep disordered breathing and suppurative lung diseases, like Cystic Fibrosis (CF).

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Innovation Grant 2018

Project Title: Detailed characterisation of structure-function relationships in mild cystic fibrosis lung disease and validation of an ultra low dose high resolution CT (HRCT) scanning protocol

Name: Paul Robinson

Institution: Children's Hospital Westmead, NSW

Value: $80,000

Duration: 1 year 

Summary:  Cystic Fibrosis (CF) is a life limiting condition causing mucus build up and infection within the lungs, ultimately resulting in death due to respiratory failure.

One approach to improve survival focuses on the accurate detection of early CF lung disease to facilitate earlier treatment intervention. Traditional tools have limitations in this setting, but newer techniques exist which are more sensitive, such as Multiple Breath Washout (MBW) and CT scanning.

However, the optimal way to use them remains unclear and the radiation associated with CT scanning remains a concern for CF physicians. This work uses advanced analysis approaches to improve our understanding of the changes that occur in early CF lung disease during childhood.

We will describe how the detailed information gained from these tests can be better used to detect early disease, and investigate the utility of ultra low dose CT scanning approaches in this setting to alleviate radiation concerns. Our assembled research team, with international expertise across these techniques is ideally positioned to carry out this work.

The results of study will provide vital help in early detection of CF lung disease, enhancing our ability for early treatment intervention and improved outcomes.

Reports:  Six month report and Final Report

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Innovation Grant 2018

Project Title: Novel Multi-Omic Insight into Evolution of Antibiotic Resistance in Psudomonas aeruginosa (PA) in Cystic Fibrosis (CF) and Relationship to Clinical Outcomes

Name: Dr Ama-Tawiah Essilfie

Institution: Lung Infection and Inflammation Group at QIMR - Berghofer Institute of Medical Research, QLD

Value: $80,000

Duration: 1 year 

Summary:   Multi-antibiotic resistant (PA) is commonly found in CF patients. Persistent infection with PA is associated with worsening lung disease and  more frequent hospitalisations. Resistance may be naturally occurring or be acquired following years of exposure to antibiotic therapy, making PA very difficult to treat.

Many people with CF are infected with epidemic, antibiotic multi-resistant strains of bacteria. Despite progress in understanding antibiotic resistant mechanisms, little has changed in how antibiotics are prescribed. Using state of the art gene sequencing techniques, this project will investigate why antibiotic resistance is so common in epidemic PA compared to non-epidemic strains and whether this increased resistance causes more severe disease.

Additionally, the project will investigate the potential of a new technique for quantifying antibiotic resistance in sputum as an improved method of antibiotic selection compared to conventional methods. If successful, this could lead to improved clinical outcomes and shorten hospital stays.

Reports:
6 month Report
Final Report

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Ann Maree Bosch Career Fellowship 2018

Project Title: Cystic fibrosis airway gene therapy: towards first-in-human clinical trials

Name: Alexandra McCarron

Institution: Cystic Fibrosis Airway Research Group (CFARG); Children’s Hospital, Adelaide SA

Value: $10,000

Duration: 1 Year

Summary: Cystic fibrosis (CF) affects many organs, but the lung disease is the major cause of morbidity and mortality. Our primary focus at the Cystic Fibrosis Airway Research Group (CFARG) is to develop a gene-addition therapy, to prevent, halt, or improve treatment of CF lung disease – for people with any CF mutation type. By introducing a correctly-functioning CFTR (cystic fibrosis transmembrane conductance regulator) gene into the airway cells, and creating functioning CFTR protein, lung health should be dramatically improved.

The CFTR gene is delivered to the airway cells using a specialised gene delivery vehicle known as vector. As pre-clinical studies progress, an important translational step is developing a way to produce the large volumes of gene vector required for human clinical trials and eventual commercialisation.

Reports: Final Report

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Abbie Fennessy Memorial Fellowship 2018

 (supported by Technipro-Pulmomed Pty Ltd & Cystic Fibrosis Australia)

Project Title: High intensity interval training using telehealth for adolescents with Cystic Fibrosis

Name: Anna Middleton

Institution: The Children's Hospital at Westmead

Value: $ 5,000

Duration: 1 year

Summary: Improvements in the management of pulmonary and gastrointestinal manifestations of cystic fibrosis (CF) have seen life expectancy increase dramatically. The emergence of secondary complications that adversely affect function and quality of life are commonly seen in adolescents and adults with CF. One of these complications is skeletal muscle dysfunction [1]. Skeletal muscle dysfunction in CF manifests with reductions in muscle strength, endurance and skeletal muscle mass [1]. Skeletal muscle mass and strength are strongly correlated with peak oxygen uptake [2-4], prognosis and survival [5-8]. Compromised skeletal muscle strength, endurance and function are correlated with reduced anaerobic performance [9-11] and reduced aerobic capacity [4, 12, 13]. Aerobic capacity is a strong predictor of mortality [6-8, 14], requirement for hospitalisation [15] and quality of life [16, 17]. 

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ACFRT in conjunction with CFSA Special Grant 2018

Project Title: A novel treatment strategy for cystic fibrosis S. aureus-associated chronic rhinosinusitis

Name: Professor P-J Wormald

iInstitution: Adelaide and Flinders Universities 

Duration: 1 year

Summary: Chronic Rhinosinusitis (CRS) is one of the most common manifestations in patients with Cystic Fibrosis (CF) contributing to CF lung disease. The frequent and often long-term use of antibiotics to treat relapsing airway infections significantly contributes to the threat of Multi Drug Resistant (MDR) pathogens. There is an urgent need for the development of new treatments that are effective at eliminating infections with MDR pathogens.

Bacteriophage (phage) is a virus that targets and kills one specific bacterial species, leaving the human mucosa and commensal species unaffected. In collaboration with Ampliphi Biosciences, our team has recently successfully completed a human clinical trial to test the safety and preliminary efficacy of a phage cocktail to treat S. aureus CRS. We have further improved this treatment to develop a novel phage-based formulation that is now able to eradicate rather than reduce S. aureus including MDR S. aureus (MRSA).

This project brings together our Adelaide-based Rhinology team (Prof PJ Wormald and A/Prof S Vreugde) with CF centres located in Adelaide and at the Royal Brompton Hospital (RBH) in London. The team aims to optimise the delivery of the new formulation to make it suitable for topical delivery to the sinus region in CF patients.

Reports: None Due

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ACFRT in conjunction with CFSA Special Grant 2018

Project Title: Lentiviral Mediated Airway Gene Therapy: Is lysophosphatidylcholine required for safe and effective gene transfer in a cystic fibrosis lung?

Name: Dr Chantelle Lee Carpentieri

Institution: University of Adelaide & Women's and Children's Hospital 

Value: $30,000

Duration: 3 years

Summary: The current treatments for CF airway disease are not preventative or curative. The addition of a properly-functioning CFTR gene into affected CF airway cells is recognised as the only rational method likely to prevent, halt or treat CF airway disease, regardless of mutation type.

To facilitate gene transfer using our Adelaide-designed lentiviral CFTR gene vector, the CF airway research group has developed a unique treatment protocol, successfully tested in several animal models. This unique treatment protocol first prepares the airway to be receptive to the gene vector using an airway-conditioning compound called lysophosphatidylcholine (LPC).  

Using this two-step dosing method (gene vector and LPC), a single dose of gene vector has produced functional CFTR correction in mouse nasal airways. Additionally, we can use this approach to introduce various test genes into cells of the airways of rats, sheep, ferrets and other animals. Despite the absence of safety issues due to LPC in these species, the safety of LPC in a CF lung has not yet been tested due to lack of an appropriate CF animal model. Now that our research group has established a CF rat colony in Adelaide, the aim of my project will be to test the safety and efficacy of our gene transfer methods for potential future use in the treatment of CF lung disease.

Reports: None Due

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Antimicrobial Resistance In Cystic Fibrosis 2018

International Task force

The prevalence of antimicrobial resistance (AMR) among microbial pathogens is increasing and is a high priority worldwide for interventions from antibiotic stewardship to new antibiotic development (http://www.who.int/antimicrobial-resistance/en/).  Increasing AMR prevalence is driven by the widespread use of antibiotics.

AMR is commonly encountered in bacteria and fungi isolated from the airways of people with cystic fibrosis (CF).  This is an expected finding given the high use of antibiotics in CF patients. The increasing survival of people with CF will result in greater lifetime exposure to antibiotics.

There is a lack of full understanding for stakeholders including people with CF, clinicians, the pharmaceutical industry, and (drug approving) regulatory bodies, about the relevance of AMR and how this should influence drug development and usage in the treatment of CF lung disease.

The Taskforce will develop guidelines on the interpretation of AMR for clinical care in CF. The Taskforce will also provide guidance on the role of AMR in clinical trials with new antimicrobial agents. The Taskforce that will have international and multidisciplinary representation will address the following objectives:

• Understand how chronic infections differ from acute infections with respect to the microbiological assumptions regarding AMR.
• Describe current and developing methodologies for determining antimicrobial resistance.
• Assess the value of current susceptibility testing including the frequency and timing of testing.
• Offer guidance for the use of antimicrobial resistance testing in the conduct of clinical trials by the pharmaceutical industry and regulatory agencies.
• Set key research priorities for the development of appropriate future application of AMR diagnostics to improve patient outcomes.
• Explore how monitoring antibiotic usage impacts on AMR in people with CF.

Australia/New Zealand Representatives

• Cass Byrnes, CF pediatrician
• Jason Roberts, pharmacist
• Tim Kidd, microbiologist
• Scott Bell, adult CF physician

Update February 2018

Thanks again to CFA for their support of this international working group. The working group met at the North American CF Conference and had approximately 50 to 60 participants.

Five groups have been established:

1. Antimicrobial resistance definitions 
2. Literature review and development of current evidence 
3. Antimicrobial stewardship 
4. Education for clinicians, patients, families and participants 

Since that meeting, the Steering Committee Group have had a teleconference to report the update. All four groups are demonstrating rapid progression. The aim is to meet again in Artimino in September 2018 in order to finalise the recommendations of the working group for antimicrobial resistance in cystic fibrosis.

Findings of the groups are anticipated to be presented in a symposium of the North American CF Conference in Denver in October 2018 and again in the European CF Conference in Liverpool in June 2019. 

At least three publications are likely to be generated by the working group but importantly will provide the clinician, research and patient community with an update on AMR in cystic fibrosis.

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Innovation Grant in Partnership with Cystic Fibrosis Research Limited (QLD) 2017

Title: RNA therapeutics: novel paradigm in mutation independent CF therapy

Name: Shafagh Waters

Institution: University of NSW (UNSW)

Value: $ 70,000

Duration: 1 year

Summary: Cystic fibrosis (CF) is a genetic disease, most common among people of European ancestry, afflicting ~70,000 individuals worldwide. It is caused by defects in a single gene that codes for the CF Transmembrane Regulator (CFTR) protein. Historically, therapies were restricted to treatment of symptoms, but new molecular therapies that restore function to the defective CFTR protein have been developed. Unfortunately, these therapies are only effective for 5% of people with CF.

This project examines how a gene (called BGas) can be genetically manipulated for CF therapy. When BGas is removed from the cell, CFTR function is restored. This therapy will be beneficial to majority of CF patients around the globe – not just 5%.

Miniaturized versions of CF patient gut (mini-gut), using their own cells as starting material are created in the lab. followed by BGas-removing compounds being added to the “mini-gut” to identify those responsive to BGas therapy.

The invaluable results from this project could drive future trials, delivering BGas-removing compounds directly to the CF patients. A similar approach has had promising outcomes for children with spinal muscular atrophy. The discovery of BGas-removing compounds may finally offer light at the end of the tunnel for CF therapy.

Reports:

• 6 month report
• Final Report

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Innovation Grant 2017

Project Title: Investigating the role and therapeutic targeting of iron in cystic fibrosis

Name: Jay Horvat

Institution: University of Newcastle, NSW

Value: $80,000

Duration: 1 year 

Summary: Whilst improved therapeutic strategies have become available for CF, many patients still frequently experience exacerbations of disease that result in progressively increasing lung pathology and deteriorating lung function.

Infections play an important role in this progression of CF with persistent Pseudomonas infections a major contributor to CF morbidity and mortality. More effective strategies are desperately needed to improve efficacy for the treatment of Pseudomonas infection in CF in order to improve patient outcomes.

Studies have shown that iron levels are increased in the airways of CF patients and increased iron stimulates Pseudomonas biofilm formation, aggregation, adhesion and invasion, allowing the pathogen to avoid host removal. Indeed, in clinically stable CF patients, there is a strong positive correlation between sputum iron and Pseudomonas levels. These findings suggest that increased iron in CF patients is a potential causal factor of Pseudomonas persistence.

In this new study, we will use a novel combination of experimental models of increased iron loading in the lung and Pseudomonas infection and clinical investigations to better understand the role of iron in the pathogenesis of CF. We will also determine whether therapeutically suppressing increased iron levels in the airways improves the clearance of Pseudomonas infection from the lungs

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Hardie Foundation Scholarship - WA Top Up Grant 2017

Project Title: The role of Interleukin and necrosis leading to neutrophilic inflammation in children with cystic fibrosis.

Name: Samuel Montgomery

Institution: Telethon Kids Institute WA

Value: $ 37,500

Duration: 3 years

Summary: This study aims to determine whether inflammation resulting from cell death in the airway is increased in early lung disease in Cystic Fibrosis (CF). It also aims to identify differences in specific gene pathways during inflammation resulting from cell death in the CF airway.

Reports: Final Report

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CFWA Golf Classic Scholarship - WA Top Up Grant 2017

Project Title: Personalised antisense oligonucleotide therapy to correct CFTR function in Cystic Fibrosis patients.

Name: Kelly Martinovich

Institution: School of Paediatrics and Child Health, Princess Margaret Hospital WA

Value: $ 37,500

Duration: 3 years

Summary: Current on the market small molecule therapies do not help all patients with CF, since it is caused by over 2000 different mutations. Here, we aim to develop therapies that target the more rare CF mutations. Many mutations change the message that is passed on from the CF gene. This faulty message results in a poorly functioning CFTR channel. The CFTR channel maintains the airway surface liquid in the lungs that helps clears infections.

The therapies that we will aim to develop are another type of small molecule called antisense oligonucleotides (AOs).  AOs can change the faulty message transferred from gene to protein and improve the function of the CFTR protein. Furthermore, AOs can be designed to target a specific site in the CF gene depending on the location and effect of the CF causing mutation that the specific person holds. In predicted cases, AOs in theory could reduce the severity of CF. It is hoped that this study will initiate a personalised medicine pathway generating molecules that lessen the disease severity caused by specific CF-causing mutations.

Reports: Final Report

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ACFRT Top-up Scholarship 2017

Project Title: Does high intensity interval training improve fitness in people with cystic fibrosis?

Name: Abbey Sawyer

Institution: School of Physiotherapy and Exercise Science, Curtin University WA             

Duration: 3 years

Value: $ 5,000

Summary: People with cystic fibrosis (CF) who are fitter have improved quality of life and may live longer.

Currently, people with CF are encourage to exercise for 30 to 60 minutes a day, in line with recommendations provided for people who are healthy. This is often difficult to achieve due to the high daily treatment burden and competing demands in life such as work, study and family.

This project will investigate whether 10 minutes of high intensity interval training over an 8-week period improves fitness and other important outcomes such as quality of life, mood, confidence to complete exercise and enjoyment in people with CF.

Reports: Final Report

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ACFRT Top-up Scholarship 2017

Project Title: Are altered carbohydrates associated with compromised immune cells in cystic fibrosis?

Name: Harry Tjondro

Institution: Department of Chemistry & Biomolecular Science – Macquarie University

Value: $ 5,000

Duration: 3 years

Summary: This project will for the first time use biochemistry to explore the aberrant carbohydrate signatures and their functional significance on CF neutrophils relative to healthy neutrophils, an important type of innate immune cells in CF.

Advancing our understanding of the structural and functional alterations of carbohydrates in CF neutrophils will be valuable in order to unravel the underlying disease mechanisms.

This study will generate valuable, fundamental biochemical knowledge to support the generation of new immune-based therapeutics to alleviate the disease burden of affected individuals.

Reports: Final Report

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ACFRT Top-up Scholarship 2017

Project Title: Pseudomonas aeruginosa behavior in cystic fibrosis: new insights using novel super-resolution microscopy.

Name: Simone Visser

Institution: Department of Respiratory Medicine – RPAH, NSW

Value: $ 5,000

Duration: 3 years

Summary:  Pseudomonas aeruginosa and other emerging bacterial pathogens (multi-resistant Staphylococcus aureus, Achromobacter xylosoxidans, Stenotrophomonas maltophilia) establish chronic lung infections in patients with cystic fibrosis by forming biofilms in the airways. 

Biofilms are adherent, slimy layers of bacteria, which are highly impermeable and resistant to antibiotic therapy, making treatment very challenging. It is well recognised that after development of chronic bacterial lung infections, patients experience deterioration in lung function, increased flare-ups and poorer survival.  There is an urgent need to develop new effective treatments against bacteria and their biofilms.

Our group has found that innovative triple combination therapy (glutathione/DNase/antibiotic) is effective in reducing pseudomonas biofilms (Ashish Kumar et al, Frontiers in Microbiology 2017; 8:1-18).  I am now expanding that work into the emerging CF pathogens, which are typically under-studied and include achromobacter, stenotrophomonas, and methicillin-resistant staphylococcus aureus. According to recent registry data, these bacterial species are increasingly common in CF patients. Further, chronic infection with these bacteria is linked with poorer lung health. I am investigating whether similar triple combination therapy is effective against the biofilms of these bacteria.

The ACFRT Grant has allowed me to begin investigating innovative combination antibacterial therapy to treat chronic lung infections in cystic fibrosis.  The combination treatment targets bacterial biofilms (slimy layer), which is usually impenetrable and resistant to typical antibiotic therapies.

Reports: None due

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Abbie Fennessy Memorial Fellowship 2017

 (supported by Technipro-Pulmomed Pty Ltd & Cystic Fibrosis Australia)

Project Title: Airway Clearance Adherence Monitoring System (ACAMS) – development and initial benchtop trial.

Name: Nathan Ward

Institution: Royal Adelaide Hospital (RAH)

Value: $ 5,000

Duration: 1 year

Summary: As part of his PhD candidature at La Trobe University, Nathan developed an electronic device that can potentially be used for both clinical and research assessment of adherence to positive pressure-based airway clearance techniques. The device has been called the Airway Clearance Adherence Monitoring System (ACAMS).

Using the funds provided through the Abbie Fennessy Memorial Fellowship, five ACAMS units will undergo independent pressure accuracy testing against Australian standards. Following this testing, the five units will undergo an initial benchtop trial to prove their utility with PariPEP S, PariOPEP and Acapella DH devices for a one week period for each device.

If this initial benchtop study demonstrates that the ACAMS device can accurately record performance of these techniques and provide analysable data on the quality of the technique performance, these data will be used to support applications for an initial pilot clinical trial. It is envisaged that this trial would recruit adults with cystic fibrosis attending the Royal Adelaide Hospital Adult Cystic Fibrosis Service.

The Abbie Fennessy Memorial Fellowship will also be used to cover the costs for Nathan to attend the North American Cystic Fibrosis Conference (NACFC) in October 2018, where he will I will be submitting an abstract on the development and benchtop validation of the ACAMS device along with two other abstracts for presentation at the NACFC.

Reports - none due

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Special Grant 2016

Project Title: Multi-action antibiotics to treat chronic biofilm infections

Name: Michael Kelso

Institution: University of Wollongong

Duration: 3 years

Summary: Biofilms often build up in the lungs of people with CF. They contain large populations of bacterial cells and are encapsulated within gum-like materials which protect bacteria against the action of antibiotics and against the action of cells in the patient’s immune system.

Antibiotic resistance can be increased up to 1000-fold in biofilms. Associate Professor Michael Kelso from UOW together with members of his research team were the first to discover that low concentrations of nitric oxide (NO) act as a signal that triggers bacteria in biofilms to disperse. When this happens the bacteria become more sensitive to antibiotics and to the body’s immune system. This project investigates the effects of combinations of NO-releasing compounds with antibiotics (cephalosporins) to develop a new way of targeting delivery of NO to biofilms.

Reports:

• Discovery of Cephalosporin-3′-Diazeniumdiolates That Show Dual Antibacterial and Antibiofilm Effects against Pseudomonas aeruginosa Clinical Cystic Fibrosis Isolates and Efficacy in a Murine Respiratory Infection Model
• Antibiotics Special Issue: Challenges and Opportunities in Antibiotic Discovery and Development
• 24 month report
• 18 month report
• 12 month report
• 6 month report

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Special Grant 2016

Project Title: Determining factors that influence the acceptance and adoption of a gene therapy for cystic fibrosis airway disease

Name: David Parsons, Martin Donnelly & Ivanka Pritchard

Institution: University School of Health Sciences, Flinders University & The Cystic Fibrosis Airway Research Group at the Women’s and Children’s Hospital

Duration: 1 year

Summary: This grant is designed to develop an ongoing relationship between the School of Health Sciences, Flinders University (CI Prichard), The Cystic Fibrosis Airway Research Group at the Women’s and Children’s Hospital (WCH; CIs Donnelley and Parsons), and Cystic Fibrosis Australia.

The primary focus of the WCH group is on developing a gene therapy treatment for cystic fibrosis (CF), and they have expertise in molecular analyses and animal models. Flinders University provides expertise in health psychology and the understanding of attitudes and beliefs in relation to treatments and health outcomes. CF Australia is a philanthropic organisation set up for the purpose of providing support and services to people with CF, their carers and families, and funding high quality research.

The aim of this partnership is to use the combined expertise and resources of the group to assess the perceived acceptability of, and public support for, gene therapy for CF. We will use this information to obtain future grant funding to develop education programs to better inform the CF community about the risks and benefits of this type of treatment to improve the success of clinical trials.

Findings from this project will contribute to the effectiveness of our future applications for funding as we will be able to include our assessments of the feasibility of the approach from both the scientific/biological and the CF community acceptance-spheres.

Reports: to follow

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