Isaac has a fairly rare (severe) mutation of CF, which means he will not respond to the small molecule drugs that you may have heard about in the news of late, which should work for a wonderful 90% of people with CF. So what hope have we?
“About 10 percent of all CF mutations don’t allow for any CFTR protein — working or not — to be produced at all. Compounds can’t correct or potentiate a protein that doesn’t exist, so an entirely new approach is needed — one that might fix the CFTR gene itself. Vertex may be “the CF company,” but gene editing is not its expertise. So, it teamed with two companies: CRISPR Therapeutics and Moderna Therapeutics. Scientists discovered in 2014 a way to harness CRISPR/Cas9 — a mechanism used by some bacteria to prevent infection by viruses — to cut unwanted DNA from organisms, raising the possibility of doing so in people. The field has exploded since, with researchers worldwide testing CRISPR’s limits against genetic and other diseases in a kind of “scientific frenzy,” according to The New York Times. Vertex sees CRISPR as a possible pair of “molecular scissors,” acting to remove a dysfunctional CTFR gene before it is replaced with a working one – effectively curing the disease.
But CRISPR trials in CF patients aren’t likely anytime soon. “[W]e’re up for the challenge. We are working on it,” Altshuler said. “But anyone who’s serious about it realizes that there’s a multi-component aspect.”As Altshuler explained, “The DNA piece, or the correcting-the-gene piece, is the easy part.” The hard parts include editing to only affect targeted genes, while aiming at those in both mature lung cells and lung stem cells — which give rise to new cells — because cells in the lung turn over frequently. CRISPR is still in its infancy, and some scientists and bioethicists have already raised concerns about a limited understanding — and the possibility the tool might be more unpredictable than thought. A study in mice, published in the journal Nature Biotechnology in July, reported damage to genes beyond those targeted.A separate three-year research partnership was started in 2016 with Moderna Therapeutics, which specializes in a gene therapy approach targeting messenger RNA. Messenger RNA (mRNA) is involved in the transcription of genetic information, the first step in producing a protein.
“We hope it’s sooner, but we’ll work for 10 or 20 years to develop genetic therapies — or any other type of therapy — to treat those people living with CF who cannot take benefit from our small molecule or oral therapies,” Altshuler said. So, while its triple combinations appear to be zooming ahead, Vertex is with gene therapies about where it was in the early 1990s, screening for the small molecules that eventually became Kalydeco, Orkambi, and Symdeko.“I want to express … our deep commitment to completing our CF journey. We’ve made a lot of progress. We’re very proud of that,” Kewalramani said. “But we’re not going to rest until we get to all patients … our commitment is really unrelenting.”
It’s encouraging that they say they are committed, it really is. But also knowing the frustrations that come from NHS England and Vertex having yet to agree a deal which will allow people with CF access to one of their existing drugs (Orkambi) and the fact the ‘gene therapy’ was the buzz phrase when Isaac was born and yet still bears no fruit; it’s also a huge (head banging) frustration. These are as close to a cure that we can hope for right now.
We were told when he was born that the earliest we could hope for access to a treatment that would work on the underlying cause of his disease (rather than just the symptoms) was about five years. We’re 13 years and counting now, trying to keep his lungs as healthy as we can so that the treatments, when they do come, may still work for him.
So, I’m working on my next fundraising plan; we are bloody in this for the long term! Have a great day x
