Specialty Focus: Tackling Rare Mutation in CF

Advancements in the treatment of cystic fibrosis (CF) in recent years have been significant. In fact, a quick scan of the “milestones” page on the Cystic Fibrosis Foundation website will show several approvals of new therapies by the FDA, specifically starting around 2010.

And while that trend is hopeful for individuals like Emily Kramer-Golinkoff, it can get a bit frustrating. Kramer-Golinkoff has the rare nonsense gene mutation of CF, and none of the approved therapies were able to help her. That was the case then, and is still the case now.

“Back in 2011, there were some really exciting new therapies in the pipeline,” says Kramer-Golinkoff, who currently has 35% lung function and spends countless hours a day going through breathing treatments.

Emily Kramer-Golinkoff

“There were drugs that targeted underlying causes rather than just treating symptoms. All these exciting advancements were wonderful, but because of a specific genetic mutation, I fell into the 10% of the CF community that, unfortunately, they were not poised to treat.”  

It’s the reason why the now-thirty-something, who received a bachelor’s degree in communications and a master’s in bioethics from the University of Pennsylvania, started Emily’s Entourage in December 2011. Emily’s Entourage is a nonprofit organization that fast-tracks research for new drugs and a hopeful cure for nonsense mutations of CF.

To date, Emily’s Entourage has raised over $3 million and led worldwide efforts to drive high-impact research and collaboration. One example is the sponsorship support from Eloxx Pharmaceuticals, a global biopharma company focused on discovering and developing novel drugs for the treatment of rare and ultra-rare premature stop codon diseases. Premature stop codons are point mutations that disrupt protein synthesis from messenger RNA.

Eloxx’s lead product candidate, ELX-02, is targeting CF and cyctinosis patients with diagnosed nonsense mutations on one or both alleles. In clinical data released in June, ELX-02 demonstrated to restore transmembrane conductance in and promote forskolin-induced swelling of CF patient organoids carrying homozygous and compound heterozygous CFTR nonsense mutations. The early results are not just potentially good news for patients like Kramer-Golinkoff, but on a personal level, also serve as a confirmation that her

David Carillet/shutterstock.com

experience is making a difference in the lives of others, she says. 

Eloxx is using organoids, a new frontier of personalized medicine, to predict drug response in CF. Organoids are created by scraping a patient’s intestinal stem cells, and then growing them in a petri dish to figure out which drugs might work in patients with rare mutations. New drugs are tested on custom-made organoids in the lab, and if the “mini organs” puff up, it’s a sign that the cells are now correctly balancing salt and water, a major issue in CF.

Kramer-Golinkoff has been donating her stem cells to the Organoid Biobank, created by the Netherlands-based HUB foundation, in hopes of helping researchers. In fact, Kramer-Golinkoff says she was the first CF patient from the US to send her organoids to the biobank. She encourages others to donate theirs as well, to help build a “toolbox” of cells for researchers. 

“We are very excited about organoids as a platform for testing new drugs,” Kramer-Golinkoff told Pharm Exec.

Eloxx gets its organoids from the HUB biobank. The donations, which are anonymous, are a critical component to Eloxx’s research and a potential game-changer for CF treatment, according to Dr. Pedro Huertas, the company’s chief medical officer. “The use of patient organoids from the HUB is rapidly being adopted as a potential surrogate marker likely to predict potential clinical benefit in cystic fibrosis patients by industry, payers, and regulators,” he told Pharm Exec. 

Michelle Maskaly is Pharm Exec’s Senior Editor. She can be reached at michelle.maskaly@ubm.com and on Twitter at @mmaskaly