CF Research

WHAT’S NEW IN CF RESEARCH?

In 2002, the CCFF funded 50 projects targeting an extensive range of questions related to cystic fibrosis. A few of these programs are highlighted below.

CF-RELATED DIABETES

Improved survival in cystic fibrosis has led to greater appreciation of complications associated with the disease, among the most common of which is CF-related diabetes, currently affecting almost 25% of adults with CF. While it is understood that diabetes, by upsetting the body’s protein balance, can produce progressive wasting of muscle mass, it is not known whether this problem reflects the breakdown of proteins, or an inability to produce new proteins.

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CF AND EXERCISE

Past studies have demonstrated how lung function, nutritional status and bacterial infections affect the survival of individuals with CF. Dr. Allan Coates (Toronto) is attempting to establish whether physical activity is a predictor of a positive change in pulmonary function. Exercise capacity, nutritional status, and pulmonary function data will be used in the analysis. Findings from this study could lead to future clinical trials.

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INFECTIONS IN THE CF LUNG

Pseudomonas aeruginosa is a class of bacteria that normally presents no threat to people. Generally, only burn victims, and individuals with comprised immune systems, such as persons with AIDS, are vulnerable. Yet for individuals with CF, P. aeruginosa is resistant to most antibiotics, and represents a constant and imminent threat to health. CF lungs are highly susceptible to infections by this bacterium, and to the ensuing cycle of infection and inflammation that does irreparable damage to fragile lung tissue.

In 2002, Dr. Joseph Lam (Guelph) was awarded the Zellers Senior Scientist Award, named in appreciation of Zellers’ outstanding leadership in the fight against CF. Dr. Lam is currently investigating changes in the surface coating of P. aeruginosa, which are related to different stages of chronic lung infection.

In order for P. aeruginosa to grow, colonize, and survive in the adverse environment in the lungs, these bacteria must have control over their genes. Dr. Doug Storey (Calgary) aims to determine how P. aeruginosa bacteria control the production of their virulence factors in the lungs, in order to be able to develop new antibiotics that specifically target these systems.

Individuals with CF are also prone to infections with the bacterium Burkholderia cepacia complex. This bacterium causes serious respiratory infections and is a major health risk for individuals with CF. Colonization with B. cepacia complex can lead to chronic infection and rapid deterioration of lung function and eventually result in “cepacia syndrome”, a lethal pneumonia. So far little information is available on the mechanisms by which this respiratory pathogen causes disease.

For bacteria to survive in humans, the absorption of iron is necessary. Dr. Pamela Sokol (Calgary) is investigating how B. cepacia complex absorbs iron to determine whether interference with iron uptake would conceivably prevent bacterial growth. Her objective is to understand how B. cepacia complex uses iron, in order to develop therapies that might inhibit iron uptake, and prevent bacterial growth.

In 2002, the Foundation awarded $5.2 million in grants to CF researchers.

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SPARX- Special Programme in Applied Research and Therapy

In 1996, the Canadian Cystic Fibrosis Foundation launched its largest research initiative, the Special Programme in Applied Research and Therapy (SPARX), designed to hasten the development of new treatments for CF.

Standing at the juncture between scientific and clinical research, SPARX enlisted some of Canada’s most talented medical investigators, who endeavored to turn promising research leads into new therapies, and combat the chronic cycle of lung infection and inflammation in CF. The development of an idea into a clinically useful drug usually requires on average 15 years of hard work, and an investment of over $200 million dollars, an impossible sum for a charitable organization to fund.

Under the direction of Dr. Andre Cantin, Professor, University of Sherbrooke, the first phase of SPARX, or SPARX I, represented a multidisciplinary endeavor involving some of Canada’s most outstanding CF investigators. SPARX I focused on furthering the understanding of airway infection and inflammation characteristics of lung disease in cystic fibrosis. In five years, the members of SPARX I have applied for patents on twelve new technologies pertaining to CF. But more importantly, SPARX members have succeeded in effecting the technological transfer of two programs, towards clinical trials:

Dextran, for which the technology has been transferred to the Canadian company BCY LifeSciences Inc., is preparing for Phase II clinical studies in 2002.
The antiprotease, Prolastin®, which, in collaboration with Bayer Canada Inc., is nearing completion of Phase II clinical trials.

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SPARX II

The objective of SPARX II was to develop safe and effective methods of gene therapy for persons with CF. In a general sense, the goal of gene therapy is to replace a defective gene with a healthy version of the same gene. Despite significant achievements in this field of research, certain obstacles have been identified, and need to be overcome before gene therapy can be routinely used in humans. With respect to gene therapy in the lung for disorders such as CF, the healthy gene may encounter many physical and physiological barriers that are part of the body’s defense systems against invading microbes while traveling to the target cells lining the inside of the lungs. To overcome these barriers and enhance its effectiveness, the healthy gene is inserted into a carrier and wrapped in a protective layer making it more resistant to breakdown by the body’s defense systems. The SPARX II team has concentrated its efforts on the use of liposome’s (fat capsules) to protect the healthy CF gene (known as CFTR) and allow it to reach and enter the lung cells containing the defective CF gene.

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