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

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.

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.

[adrotate group=”1″]

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.



28 comments

    • Stephen Shannon says:

      That is an excellent question. To give a little background for other readers, Cystic Fibrosis results from around 2,000 different mutations in the CFTR gene. The mutations are grouped into six different classes based on how the mutation effects the production and processing of the CFTR chloride channel.

      Unfortunately, I have had a difficult time finding literature on the RNA Therapy. I believe the current drug QR-010 is specific for homozygous F508del, so it would be applicable to class II mutations. The RNA oligonucleotides target repair of pre-mRNA in the nucleus so I would assume that with refinement of the therapy it could theoretically target mutations which produce an mRNA transcript. It would then follow that it could potentially be used in class II-VI mutations, but not class I since it results in a premature stop codon in the gene.

      I am sorry I don’t have a more direct answer for you. This article, PC Zamecnik, MK Raychowdhury, DR Tabatadze, HF Cantiello Reversal of cystic fibrosis phenotype in a cultured AF508 cystic fibrosis transmembrane conductance regulator cell line by oligonucleotide insertion Proc Natl Acad Sci 2004 101(21) 8150- 8155, may give you better insight into explaining the technique in vitro.

      • Mallika says:

        Thanks for the reply. when might QR 010 hit the markets if all goes well. Appreciate any information on this. May be an article seperately on ProQR will help us alot. I put the same questions in ProQR site and they did not respond. I am from India and my 4 year old is diagnosed with CF when 2. A science grad as I am, I educated myself about this and had to be ahead of the doctors here who do not understand the problem well enough. Being in India where the availability of meds is a big question, i sometimes panic but I derive hope from articles and positive information like this. As you correctly put Dum Spiro spero.

        • Stephen Shannon says:

          Mallika, I believe that the QR-010 is preparing to begin phase I clinical trials. Again, I have had difficulty finding literature regarding the drug. Pharmaceutical companies tend to be tight-lipped regarding their research. As I learn more I intend to write an article regarding its progress. Hopefully we will get more information in the coming months.

          I think your education regarding your son’s diagnosis of CF is wonderful. I think it is so important for patients and families to be well informed regardless of their location. We should be educated to be able to better connect with our doctors to ask to the right questions. Dum Spiro Spero

  1. sandra weinholzer says:

    Hi, Excellent article! The objectives for correct treatment of cycstic fibrosis is pulmonary hygiene hard hand percussion all lobes daily and bronchodilators with mucomyst. This daily treatment moves the mucous out of the airways, preventing plugging and damage to the lungs!! And helps keeping you out of the hospital!! From a Respiratory Therapy Practioner whom has worked with CF 1975- 2015 and contining to follow! Thank you Sandra Weinholzer RCP

    • Stephen Shannon says:

      Sandra, I would love to hear your thoughts on hand percussion versus using a machine such as Hillrom. I have always thought hand percussion more effective. Do you know of any research that compares one versus the other?

  2. Donna Anderson says:

    Excellent! The words “Just Breath” live with me everyday. I am a Registered Respiratory Therapist and these two words mean everything to me. My son was born 27 years ago and was diagnosed with CF on that day. My world turned upside down. A very emotional time for my family. My husband and I decided to raise our son in a positive manner. Never letting CF define who he is. His health stays very good even today. I’m very proud of my son who will graduate in August with his PhD in biomedical science. He is married to his high school sweetheart and have a great life together. As an RRT, I have see the rage of this awful disease. So excited for the new drugs that are becoming available and the impact it will make on our CF community. So for now “Just Breath”.

  3. sharon says:

    my son is 34 and was diagnosed with cf when he was 3 months of age the doctor told me he would not live past 1 year old.but he has he has been very well not haveing to go in to hospital since he was 10.but the last 3 years he has become ill and haveing to go into hospital and be put on iv .. i dont understand all these diffrent strans of cf how can i find out what strain my son has..i like the saying while you breath you hope…x

  4. Damon says:

    Great article Stephen. It’s inspiring to hear insights from someone who battles the disease and who is also so engaged in efforts to research potential therapeutic treatments. Regarding the 2000 mutations in the CFTR gene, how do you see the future of treatment variation based on a haplotype analysis of these mutations? Also, in some literature I have read where some patients who are essentially CF “phenocopies” do not have any mutations in the CFTR gene. How much research, both academic and industry based, is being carried out for these patients?

  5. W. Hoh, MD MPH says:

    Kalydeco has worked extremely well for my six year 9 month old son who has cystic fibrosis. G55/dF508 mutations. In fact, It has gotten to the point that he has now Put on so much weight that we are going to have to start to calorie restrict his high fat diet. He is putting on too much weight. I never thought I would have to put my son on a diet. But we do live in West Virginia, the most obese state in the nation, so I guess he just wanted to fit in. Lol. I am the happiest man on earth.

    The ultimate irony is that I started out in a Pediatrics residency, but switched out when I couldn’t deal with a patient dying of cystic fibrosis when I was on call. It was too difficult emotionally. I switched into Occupational medicine, which deals with work related injuries and illnesses such as coal workers pneumoconiosis, Workers compensation injuries. Can I get married and have a son with cystic fibrosis. And I take him to the same hospital where I was a resident in pediatrics.

    Things happen for a reason in this world. God bless you and keep doing your research. I’m sure that you will help people in this world but what you do. And may the Kalydeco Combination help you as much as it has helped my son. The difference has been night and day.

  6. Heather says:

    That was a great article. My son (born 1988) has CF and we understand fully the uncertainty of this disease. There are no promises. We have an older son (born 1986 – a carrier) and a younger daughter (born 1993 after the CFTR gene was identified – also a carrier). We hoped for wonderful progress when our son was born also. He is doing very well and works full time as a computer tech in a local secondary school. He has one copy of the G551D mutation and was asked to take part in a trial just over a year ago … the drug has finally been listed on the PBS scheme here in Australia. After a year on the drug we do not see a dramatic change but we slowly begin to realise that, yes, he is not coughing like he used to and he is managing to get to the gym nearly every evening and his appetite is improving all the time. This is a profound step forward and we hope the research continues to help all the cf community worldwide. Thank you for your wonderful insights and informative article on this great breakthrough and we wish you all positives in your journey ahead.

  7. Dan Casey says:

    Third time reading this. Such an inspiration.

    “The Spirit of God has made me, and the breath of the Almighty gives me life.”
    Job 33:4

  8. Hasan Tahir Abbas says:

    My two months daughter, our first child tested positive with CF in her initial blood screening. The whole news came as a devastating shock upon us. While we are praying for the sweat test to come out negative, we are preparing for the worst. Stephen, it is people like you who spread rays of hope and comfort, and I am truly grateful to you to come up with this consolatory article.

    • Brittany Britton says:

      Prayers for your family! My son is 12 weeks old & we found out at his 1 month (5 weeks old) checkup that he tested abnormal for CF. I know the initial news can be really scary but don’t lose hope. They have came so far with treatments for this disease which make it manageable. Just remember it could always be worse! My son ended up having CF, as of right now he takes Creon before every bottle to help break down his food & absorb the nutrients & we do his airway clearance by hand in the mornings & before bed. Regardless, your family will get through this! Sending positive vibes your way!

  9. Debra says:

    I am here just to offer a little ray of hope. My brother has CF. I don’t know off hand which mutation it is, just that he has the more extreme strain. He is 41, he is married with two children and has a fantastic (& demanding) job. We have always remained positive around him and so has he. His has always remained very active, engaging in daily sports. He had a bad run about 5 years ago with pneumonia (it was the worst he has ever been) but he pulled through it and is doing well. I think his kids give him a focus to stay committed to maintaining his health.
    When he was born, there was no hope that he would live past 10 or 12, but here he is today at 41! Miracles do happen! So please stay positive and committed

  10. mary cassidy says:

    my beautiful great grandson max was diagnosed with CF shortly after birth, and it broke our hearts and came as a dreadful shock.
    at the moment he is doing well, but has spent a lot time in leeds infirmiry. My only wish is that a cure is found for this dreadful disease, and my lovely little max can grow up without CF.I pray everyday that a cure will be found.

  11. Lucy says:

    Hi
    I have a precious niece with CF…….and a new acquaintance i have recently made claims to have cured her own 2 CF children through purely dietaru means…..persobally i doubt this but she swears specialists made the diagnosis when they were little but that her adult children are now without CF…she told me scientists now know you can change genes through diet

    Have you heard these type of statements before?..cf cured through diet..could there be any truth to any of what she says?

    • Jessica says:

      I don’t know about my genes but I was diagnosed at three months. I’m 20 now and I know that after several years of focus on my diet and environment, my sweat chloride test is negative for CF, I don’t have any vitamin or other deficiencies (I used to have the typical ADEK and also low iron), my lung function is at 112% predicted, and my nasal polyps, which I’ve had surgically removed twice before, are now shrinking on their own and aren’t a problem. The only meds I use anymore are nebulized saline (the over the counter one, not even prescription) 1-2x/wk and a sinus rinse almost every day. I don’t do the vest or anything, but I do play the flute and I am always laughing so I’m sure that helps. I think there could certainly be truth to what your friend claims, it’s just believed to be scientifically impossible at this point with our knowledge base and that makes it less certain, so nobody is prepared to stand behind it. My hope is that all these little “impossible” success stories will help get the research moving faster so we can all be cured!

  12. myra says:

    Good luck Stephen and to all the other who are affected by this condition. My daughter’s classmate , who is only 20, has CF and my heart goes out to him . However I have hope that in a few years a cure will be found, I choose to remain positive!

  13. Dominique says:

    My best friend passed away on Monday due to CF and I honestly wish I knew more about this disease and seen this article before hand.

  14. Barish says:

    Hello Stephen, thanks for such a nice article with such promising findings with regard to CF. I’ve just found out that my best friend’s newly born daughter was diagnosed with CF which provokes extreme anxiety for her parents and us, those who try to obtain as much information as possible in order to encourage them and give all the support they need. I do hope there will be a cure soon for all patients. I’ll keep on following your updates, once again thank you so much for your efforts.

  15. joe says:

    The cure for cystic Fibrosis will be found.

    How do I know? That’s easy… I asked God and I know that my prayer was heard and will be answered.

  16. Donna says:

    Thank you so much for those words Stephen, my daughter is expecting any day now. She carries F508 and her husband R117H with a negative 5T. I am praying our sweet baby will not have CF but I have to say I am terrified as her grandmother and today I just needed words of encouragement and I see the words you typed above. It was a miracle today to read this and I have never needed anything more than that,and I know that no matter what you are right and I know our prayers will be heard and answered. Thank you for your encouragement and God Bless!!

  17. Dear Stephen and everyone,

    I am the father to a 15 months old son with CF who was diagnosed at age of 2 months. We live in Kabul – Afghanistan where the CF patient was not seen before and we are currently importing all his medications from India while we take him there twice a year for monitoring. These costs me by more than 80% of the family income which makes the life extremely difficult for me, my wife and 2 other children.

    I have tried to contact CF organizations to get help and guidance to manage my child’s condition; including the world one, with no success. Country specific organizations are saying that they only help the in-country patients while the world one has not responded at all!

    We are looking for the support options below:

    1. Get access to a periodic visit to a specialty center for CF to monitor his condition where we would only afford the travel and accommodation costs (looking for a social welfare funded medical treatment cost)
    2. Help in finding a used vest on donation or with a reasonable price
    3. To become part of a treatment trial with a reputable research organizations on CF
    4. Any information and support in regards to a possible immigration to a country with the CF related available currently medical services
    5. Any kind of advice or support would be appreciated as there is not a single specialist for CF in the region – including India where they only check for symptoms of CF only

    Thanking you all,

Leave a Comment

Your email address will not be published. Required fields are marked *