Q&A: Genetic technologies aim to advance cystic fibrosis treatments

Key takeaways:

• The Cystic Fibrosis Foundation is providing funds to Prime Medicine to advance research on its gene editing technology.
• This technology could have a major impact on future cystic fibrosis treatments.

In patients with cystic fibrosis, a new genetic technology could permanently fix the CF transmembrane conductance regulator gene in hundreds of disease-causing CF mutations, according to a press release from the Cystic Fibrosis Foundation.

Prime Medicine is conducting research on what is known as gene editing in CF, thanks in part to funding from the Cystic Fibrosis Foundation.

Notably, the funds are dedicated to research on two of Prime Medicine’s platform technologies with hopes that the editing technology can make both small and large adjustments to the CF transmembrane conductance regulator (CFTR) gene.

To learn more about gene editing and what this funding means for all people with CF, Healio spoke with Steven M. Rowe, MD, executive vice president and chief scientific officer of the Cystic Fibrosis Foundation.

Healio: What is gene editing?

Rowe: Gene editing uses the cell's own DNA repair machinery to correct the mutation in the cell’s DNA. In CF, gene editing corrects the disease-causing mutation in the CFTR gene, resulting in a potentially permanent fix to the CFTR gene. Unlike other types of genetic therapies, a gene editing approach would likely not need to be re-dosed.

Healio: How could research in gene editing advance CF care?

Rowe: CFTR modulators, which are treatments that address the underlying cause of CF, help the CFTR protein function properly, which for many has led to dramatically improved lung function and other benefits. Despite improvements for many who take modulators, they are not a cure, and the effects of the disease can persist. In addition, 10% to 15% of people with CF either cannot benefit from them because the mutations that cause their CF won’t respond, or because they cannot tolerate the side effects.

Since gene editing therapies would potentially permanently fix the root genetic cause of CF, gene editing represents one of the most promising approaches to developing a cure for CF.

While a curative treatment would not be able to fix existing organ damage, depending on the stage of disease, it may be able to stop CF from progressing.

Healio: What specific CFTR mutations could be corrected through this research? How many people have these types of mutations, and what is known about the demographics of these populations?

Rowe: The work with Prime Medicine has the potential to benefit people with CF who have any of the more than 1,700 disease-causing CF mutations. We are funding two approaches Prime Medicine is pursuing.

The first is a targeted approach that can address mutations with technology that appears to be working well in the lab. This technique replaces a small number of bases where mutations are frequent with the correct, normal sequence. When performed in areas where mutations frequently occur in the gene, it may be applied to many — but not all — CFTR mutations.

For the second approach, a large, functional piece of DNA would be inserted into the CFTR gene. This large insertion would address the majority of CF mutations.

Cystic fibrosis can affect people from any racial and ethnic group. However, people of color are more likely to have nonsense or rare mutations that don’t respond to CFTR modulators, making it more likely that their CF disease will progress. The CF Foundation has committed to advancing research that would provide treatments and ultimately a cure for CF for all people with CF. The CF Foundation will continue this work until every person with the disease has a cure.

Healio: What are some of the challenges in delivering genetic therapy to people with CF? How will gene editing research address these issues?

Rowe: If a genetic therapy isn’t successfully delivered to the correct cells in the body, the edited CFTR gene can’t do its job of restoring CFTR function. Delivery challenges include the body’s natural defense mechanisms blocking entry of a genetic therapy, a potential therapy being too large for an available delivery vehicle and a potential therapy not targeting the correct cells, among others. The CF Foundation is funding many programs focused on delivery of genetic therapies so that we can address these various challenges.

Healio: What does the funding mean for all people with CF?

Rowe: Prime Medicine’s research is in its early days. However, there are three key reasons why this investment is exciting for CF.

First, Prime Medicine is developing two distinct approaches to make both small and large edits to the gene. This combination of approaches would help address all mutations of CF, no matter where they occur in the CFTR gene. This would mean that no matter what CF-causing mutations a person with CF has, there would be a potential gene editing therapy that could eventually address any individual’s cause of disease.

The second is that this could result in a permanent fix to the CFTR gene. If Prime Medicine’s potential therapy is successful, it may only need to be administered one time.

Finally, we are not only looking forward to seeing the promise of Prime Medicine’s technology in CF, but we are excited for the potential of it to be applied to other genetic diseases, especially those for which there are not yet treatments.

Our investment in Prime Medicine is part of our strategy to fund multiple promising therapies at once to address the genetic cause of CF. You can see the other treatments we are supporting on our drug development pipeline, which includes mRNA treatments and other genetic approaches that may potentially treat the lungs of people with CF, regardless of their CFTR mutations.

Reference:

• Cystic Fibrosis Foundation funds up to $15 million to Prime Medicine to pursue gene editing in CF. https://www.cff.org/press-releases/2024-01/foundation-funds-15m-prime-medicine-gene-editing. Published Jan. 25, 2024. Accessed Jan. 25, 2024.