The magical trident targeting CF

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The FDA approved Trikafta on October 21, 2019, calling it a “new breakthrough therapy for cystic fibrosis”. Wow — I’ll always remember the time when Barb burst into tears as she read about the approval of Orkambi on her iPhone while we were on a plane to Hawaii in July 2015. So as I said in my speech at the Taste of Utah this year: “If she were still alive Barb would literally have cried tears of joy to hear about the FDA approval of Trikafta.”

Dr. Francis Collins, who played in critical role in identifying the CFTR gene, contributed an editorial to the New England Journal of Medicine detailing the journey leading up to the development of Trikafta. It is a great read. Some excerpts that hit home for me:

The diary entry of an 8-year-old girl with cystic fibrosis indicates that Aug. 25, 1989, was an important day for her. That was the day the research teams at the University of Michigan and the Hospital for Sick Children, Toronto, announced the discovery of the cystic fibrosis gene and the most common mutation, a three-base deletion that results in a missing phenylalanine in codon 508 (denoted the Phe508del CFTR mutation).

I was a first year faculty member at the University of Colorado and Barb was in the middle of her training to become a pediatric pulmonologist on the day of that announcement. We were giddy with excitement; gene therapy will cure this disease in 7…at most 10 years. Or so we thought - gene therapy for a cure continues to be maddeningly elusive. But until gene therapy is a reality, how about trying to nudge the abnormal CFTR protein to work like it’s supposed to work:

We hoped that the gene discovery would someday lead to effective treatments for children and adults with cystic fibrosis, but we knew that would be a long road. Now, 30 years later, that time has come. The results of a pair of phase 3 clinical trials in the Journal and in a simultaneous publication in the Lancet document impressive benefits from triple-drug therapy for persons with cystic fibrosis and at least one copy of the Phe508del CFTR mutation, who represent approximately 90% of persons affected by this life-shortening autosomal recessive disease.

Chillzzz…and cure by gene therapy is still a pressing goal:

This should be a cause for major celebration. Yet we must not abandon the patients with cystic fibrosis who have null mutations and will not have a response to these drugs. Even beyond that, the “best day ever” for all of us traveling down this long road together will be the day when the more than 70,000 persons with cystic fibrosis worldwide do not need to take drug therapy at all and there finally is a permanent cure for cystic fibrosis that works for everyone. Although the challenges are substantial, one can imagine such an ultimate approach involving in vivo somatic-cell gene editing of airway epithelial cells.

We’re fortunate that many very smart and dedicated people continue to work towards a cure for all those affected with CF. Dr. Collins closed the editorial with this heartfelt statement:

Shortly after our identification of CFTR, I wrote a song entitled “Dare to Dream.” The lyrics expressed hope that the gene discovery would lead to effective treatments for cystic fibrosis — that someday we would see “all our brothers and sisters breathing free.” It is profoundly gratifying to see that this dream is coming true.

Wait - Dr. Collins not only is the head of NIH, co-discoverer of the CF gene, led the Human Genome Project, received the Presidential Medal of Freedom and National Medal of Science…he’s also a Singer-Songwriter?! Yup - here’s the proof:

Postscript: Hopefully I won’t be thrown in jail for violation of the DRM music copyright law by posting this video. Just in case though, you may want to contribute to the “Get Derek Out of Jail Fund