Breakthrough On Cystic Fibrosis One Step Closer As New Research Alliance Formed
Article Date: 27 Jan 2011 – 3:00 PST

McGill University and GlaxoSmithKline plc (GSK) have signed a collaboration agreement to develop a potential breakthrough approach to treat cystic fibrosis, a fatal genetic disease. the trans-Atlantic effort between researchers from McGill’s Faculty of Medicine and their GSK collaborators in the UK, will focus on developing molecules that could treat the disease by correcting the dysfunction caused by the mutated gene. This revolutionary approach will be a departure from current treatments, which only manage the symptoms or complications of the disorder. the collaborative research is co-sponsored by the Canadian Institutes of Health Research (CIHR).

Cystic fibrosis (CF) is one of the most common fatal genetic diseases. It is a multi-organ disease but primarily affects the lungs and digestive system, causing mucous to thicken and leaving patients at higher risk of infections. CF is caused by a mutation in the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR). about 90 per cent of those living with cystic fibrosis have a particular mutant form of this gene, which makes a protein that could still work but has a defect that prevents it getting to the right place in the cell to function correctly.

Dr. David Thomas, Chair of McGill’s Department of Biochemistry and Canada Research Chair in Molecular Genetics, is an expert in protein quality control. Dr. John Hanrahan is Professor in McGill’s Department of Physiology and an expert in chloride transport and epithelial biology. they are uniquely qualified as lead investigators on McGill’s side, having conducted extensive research on the CFTR protein and have identified a number of molecules that look to restore normal CFTR function.

“If we can restore normal function to the mutant cystic fibrosis protein, we can radically transform the lives of millions of children. It will move us from treatment of symptoms to prevention of the disease and would ultimately save lives,” said Dr. Thomas. “We will now be looking at enhancing these small molecules to improve their ability to “rescue” or “correct” the mutant protein, allowing it to reach its proper location and be more active,” added Dr. Hanrahan.

“GSK is excited to be applying our expertise in areas including medicinal chemistry to this innovative area of research,” said Dr. Roberto Solari, head of respiratory biology at GSK. “We hope at the end of this two year collaboration we will have a compound that is be ready to be investigated as a potential new medicine. Collaborations such as these – where we share knowledge, expertise and resource – provide a highly effective way of progressing cutting edge research.”

“This strong collaboration between an industry partner, government granting agencies and the University is a superb example of partners building on mutual strengths and collaborating where our research interests converge,” said Dr. Rose Goldstein, Vice-Principal (Research and International Relations). “We are grateful for the support provided by GSK and CIHR, facilitating our work together to give people with cystic fibrosis a healthy and full life expectancy.” 
“Health research successes in the 21st century will be very much dependent on the ability of organizations from the public, academic and private sector to combine efforts and pool resources,” said Dr. Marc Ouellette, Scientific Director for the Canadian Institutes of Health Research’s Institute of Infection and Immunity. “In particular, this grant will increase our understanding of the cellular mechanisms causing cystic fibrosis and provide novel ways of targeting genetic based diseases. Research done through the support of this partnership will add to groundbreaking work done by Canada’s strong Cystic Fibrosis research community, including those funded under the Canadian led Human Microbiome Initiative.”

This research program has funding from both GSK and from an R&D operating grant from CIHR. It builds on previous work carried out with support from the Canadian and US CF Foundations, Génome Québec, CIHR and the Canadian Foundation for Innovation (CFI). It is the flagship project of a new cystic fibrosis translational research CFTR centre at McGill that has been established with support from the CFI.

About the Cystic Fibrosis

Cystic Fibrosis is caused by a single faulty gene that controls the movement of salt in the body. In people with Cystic Fibrosis, the internal organs become clogged with thick, sticky mucus resulting in infections and inflammation making it hard to breathe and digest food. There is no cure for the disease. about one in every 3,600 children born in Canada has CF. Treatment is aimed at controlling symptoms and infections. all disease-causing mutations in the gene for CFTR prevent the chloride channel from functioning properly, blocking movement of salt and water into and out of cells. As a result, cells that line the passageways of the lungs, pancreas, and other organs produce abnormally thick, sticky mucus. This viscous mucus cannot be easily cleared by the body, leading to obstruction of airways and glands and trapping bacteria that give rise to chronic infections.

Source:
McGill University
GlaxoSmithKline
Canadian Institutes of Health Research 
medicalnewstoday.com/articles/214887.php

MetroWest Medical Center has won town health board approval for a drug trial to treat the most common sexually transmitted infection.

With the backing, MetroWest Medical can soon join a 58-site nationwide clinical trial for a drug from pharmaceutical giant the Roche Group for human papillomavirus, or HPV.

HPV is passed through genital-to-genital contact and oral sex, with at least 50 percent of sexually active Americans getting it at some point in their lives, according to the Centers for Disease Control.

in most cases, HPV infections are not serious, and they typically go away without treatment. But some types of the virus can lead to genital warts. And some strains are the main cause of cervical cancer, a disease that kills 12,000 American women yearly and does not have symptoms until it becomes advanced.

Both vaccines on the market – Merck's Gardasil and GlaxoSmithKline's Cervarix – are recommended for girls ages 11 and 12, although they can also be given up to age 26 for those who did not receive shots earlier in life or did not complete the series. Gardasil is also approved for boys and men ages 9 to 26.

But the existing vaccines provide prevention, rather than a cure. Roche's drug is meant to treat the abnormal appearance of cells on the cervix, a condition called dysplasia that is caused by HPV and can lead to cancer. Rather than attack the virus directly, the liquid injection delivers a protein similar to one found in HPV, priming the immune system to release antibodies.

the drug is a biologic, meaning it's created not through the old method of using chemistry equipment to create medications but rather through living organisms. like most other drugs in the growing biologics category, Roche's tweaks the DNA of the organism – not publicly identified by the hospital because it's a Roche trade secret – for production.

That was the initial rub with the health board, since Framingham has an unusual bylaw dating to the late 1970s or early '80s banning the use of humans in drug trials involving genetically modified organisms.

MetroWest Medical raised the possibility of changing the bylaw with the health board or receving a permanent exemption but received a variance just for the trial instead.

"We're very satisfied with this," said Gary Johnson, MetroWest Medical's research director. "what we need to do is demonstrate this can be done safely and effectively here."

the health board decided it would proceed on a case-by-case basis, with Genzyme Corp.'s biologics not at issue because it does not test them on humans in Framingham.

Health Board Chairman Mike Hugo, a former vaccine injury attorney, said his board doesn't plan to be unreasonable when assessing clinical trial requests and just wants to stay informed.

"This presents some great opportunities for the town," he said of the trial and others that may follow.

Town Health Director Ethan Mascoop and resident Carol de Groot-Bois will sit on a hospital biosafety advisory committee, which must still sign off on the HPV trial. Once it does so, the hospital will ask for referrals from doctors. it will look to enroll eight women who are over age 18 and diagnosed with an HPV infection and more serious dysplasia. some of the women will receive a placebo, although neither they nor the researchers will know whom so the study's integrity is maintained.

"They're not being shortchanged right now, because we don't know if it works," Johnson said of the control group, who will still receive surgery when needed to remove cells on the cervix.

even if vaccinated, women still need regular pap tests to screen for cervical cancer.

(Michael Morton can be reached at or 508-626-4338.)