An Undeniable Hope: Recent CF Breakthroughs Show That a Cure Can Be Found

In his first weekly column for Cystic Fibrosis News Today, PhD student and CF patient Stephen Shannon talks candidly about what the ongoing search for a cure for Cystic Fibrosis means to him, and why there is great reason for Hope.

I was two years old when I was diagnosed with Cystic Fibrosis (CF). It has taken me twenty-five years to come to terms with the disease. I’ve spent the greater part of my life trying to convince myself I was normal, that I could lead a normal life. I did not want to confront the realities of the disease because there is currently no cure. Existing therapies are directed toward merely mitigating its symptoms. I felt I couldn’t allow myself to confront the reality of my health because I did not have any real hope that it could change.

Cystic Fibrosis is caused by a genetic mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The mutation results in a dysfunctional chloride channel, which creates an inhibition of sodium and water across epithelial cells. The reduced conductance of water results in a thick mucus, which become difficult to clear from the lungs and obstruct the airways. The immobilized mucus provide a haven for bacterial growth, giving rise to chronic pulmonary infections. Shortness of breath and severe decay of lung function become a way of life for those with CF, and they are often a prelude to lung transplantation and premature death.

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The first ray of hope in the CF community shone in 1989 when Collins, Riordan, Tsui and colleagues first identified the CFTR gene responsible for the disease. A tremendous hope surged that gene replacement therapy could soon be developed to replace the defective CFTR gene. Preliminary evidence in vitro (within cultured cells outside a living system) was promising for the development of gene therapies and an eventual cure.

The year of 1989 was not only the year the CFTR gene was identified but was also the year I was born with Cystic Fibrosis. Doctors and researchers were confident that my life would be different, free of disease. However, the hope for a cure that seemed so close at hand never came. The success of gene replacement found in the lab never materialized in clinical applications, and 25 years later me and the 75,000 worldwide living with disease are still without a cure.

A New Era of Hope for Cystic Fibrosis Sufferers

However, the past few years in CF research and treatment has brought an undeniable hope to the CF community. In his State of the Union address on January 20, President Barack Obama highlighted our tremendous excitement, proposing a new research initiative in precision medicine. “I want the country that eliminated polio and mapped the human genome to lead a new era of medicine — one that delivers the right treatment at the right time,” he said. “In some patients with cystic fibrosis, this approach has reversed a disease once thought unstoppable.”

Listening to the State of the Union Address that night as a guest of the First Lady was William Elder, Jr. William has been a long-time advocate within the CF community and is currently in his third-year as a medical student. He is also fortunate to be one of only 4% of CF patients eligible to take Kalydeco (Ivacaftor, or VX-770), the ground-breaking new therapy recently developed by Vertex Pharmaceuticals.

Klaydeco is the first treatment that directly targets the cause of Cystic Fibrosis rather than simply mitigate its symptoms. The drug is part of a group of CF modulators that are being developed whereby small molecule drugs interact with the mutated CFTR protein to allow it to function properly in the cell membrane. For me and others like me, this is the first treatment that offers real hope we may experience a life outside of sickness.

In addition to Klaydeco, Vertex is currently awaiting approval of its combination therapy of Lumacaftor and Ivacaftor (VX-770; VX-809), which was granted an accelerated review by the FDA with a target review date of July 5, 2015. The combination therapy will be eligible for patients aged twelve and older who are homozygous (have two copies) for the F508del mutation, approximately 50% of CF patients worldwide. Although these therapies do not yet offer a complete cure for the disease, they represent the greatest hope for those who have Cystic Fibrosis since the discovery of the gene twenty-five years ago.

Vertex is not the only biotech company in the game to develop these therapies. An exciting company to watch in the next few years is the Netherlands-based ProQR Therapeutics. ProQR is developing a novel RNA therapy for CF that has shown exciting preliminary results. Their drug, QR-010, is an RNA oligonucleotide that targets the CFTR mRNA in the cell, reverting the mRNA to its proper state in order to then produce a fully functioning protein. At least in theory, QR-010 could bring about complete restoration to the function of cells affected by CF.

This past year has been the first time I have allowed myself to begin to hope that my life can be different than it is now. When I was 21 I took a year leave from college to travel in Europe. During my wanderings I found a grand stained glass window that spanned two floors inside a Manor in the South of England. In the center pane was written the Latin phrase, “Dum spiro spero.” I later came to learn that the phrase translates to, “While I breathe I hope.”

Now more than ever, the words “Dum spiro spero” is the strength that is carried in each of us who suffer from this disease. And with each of these therapies that is developed, our breath becomes deeper and our hope stronger.

Stephen will be writing a weekly column on his experiences with CF. Be sure to check in every thursday for an update on his column.