Emily’s Entourage and Cystic Fibrosis Research

Emily Kramer-Golinkoff started Emily’s Entourage in 2011 with the aim of accelerating research for the last segment of cystic fibrosis (CF) patients who still lack effective treatments.

For most cystic fibrosis patients, new medications have significantly improved their quality of life, making a once debilitating lung condition much more manageable. However, there’s a catch: around 10% of patients, those with different genetic mutations, don’t benefit from these treatments.

“We have been left behind,” Kramer-Golinkoff remarked. Her organization seeks to hasten research for these “final 10%” of CF patients, who either cannot use existing therapies or face adverse effects. As the CF community convenes this week in Atlanta for its largest annual event, she aims to spotlight these patients, especially given the recent setbacks in research. In May, Vertex Pharmaceuticals and Moderna halted a clinical trial for a drug based on mRNA technology—which was, notably, the same used in COVID-19 vaccines—due to tolerability concerns. Earlier in February, Boehringer Ingelheim also discontinued a trial for a CF gene therapy.

Four decades ago, when Kramer-Golinkoff was diagnosed with CF at just six weeks old, the story would likely have ended with a failed clinical trial. Today, however, thanks largely to her nonprofit’s efforts, there are new glimmers of hope.

CF affects approximately 40,000 individuals in the U.S., leading to the buildup of thick mucus in the lungs, which can cause severe infections and respiratory failure. The majority, around 90%, have a specific genetic mutation that makes them eligible for treatments like Trikafta and its newer counterpart, Alyftrek—both developed by Vertex Pharmaceuticals. These drugs enhance the function of the CFTR protein that regulates salt and water levels in the body, effectively thinning the mucus in patients’ lungs. A recent article highlighted a major breakthrough in The Atlantic, showcasing how many patients are now participating in 10-K races and climbing stairs, activities once thought impossible.

Yet for patients like Kramer-Golinkoff, who cannot produce a fully functional CFTR protein, the major advancements haven’t made a substantial difference. Since its inception, Emily’s Entourage has raised over $22 million and sponsored 51 research projects exploring various treatment methods, including antisense oligonucleotides (ASOs), small molecules, and gene therapies.

One of the biggest hurdles scientists face is delivering drugs to the right cells, particularly since the lungs are designed to keep out foreign invaders. This challenge is compounded in CF patients, whose lungs are filled with mucus. “It’s incredibly challenging in a healthy lung,” said Chandrabali Ghose, chief scientific officer for Emily’s Entourage. “But it’s orders of magnitude more difficult in a CF lung.”

Despite the obstacles, a new gene therapy from Spirovant Sciences shows promise, as it could potentially work for any genetic variation of CF. This drug is currently undergoing early-stage clinical trials. Emily’s Entourage is also exploring treatments involving phages—natural viruses that target bacteria—and antimicrobials to combat drug-resistant infections that can threaten the lives of CF patients.

“We see these as buying-time initiatives,” Ghose added. The foundation’s efforts could also pave the way for advancements that benefit patients with other medical conditions, including those suffering from joint and skin infections. Additionally, they’re researching nonsense mutations, which occur when DNA alterations cause the premature halting of protein production, contributing to various diseases. Insights gleaned from this research may aid patients with a range of rare genetic disorders.

“We all benefit when there’s a leap forward,” Kramer-Golinkoff noted.

Many people hear about the progress for 90% of the CF community and think we’ve figured it out, but that is not true. Those in the final 10% are still contending with the same killer disease that CF has always been.

Kramer-Golinkoff finds inspiration in the case of Baby KJ, which has been a catalyst for regulatory reforms meant to allow the creation of personalized medications for individual patients. There are roughly 2,000 genetic mutations that lead to cystic fibrosis, with many being exceedingly rare, affecting just a small number of individuals.

One of her key challenges? Dispelling the notion that cystic fibrosis has been conquered, as this misunderstanding hampers investment in new treatments. “Many people hear about the progress for 90% of the CF community and think we’ve figured it out, but that is not true,” she explained. “Those in the final 10% are still contending with the same killer disease that CF has always been.”

At 41, Kramer-Golinkoff feels grateful to still be alive, especially since many CF patients at her stage are facing severe health issues or waiting for lung transplants. However, life is still a challenge for her—she relies on continual antibiotics to manage chronic lung infections, uses supplemental oxygen continuously, administers multiple injections for CF-related diabetes, and takes over 30 pills daily. All of this, just to preserve whatever lung function she has left and slow the disease’s progression.

She’s acutely aware that her story isn’t unique, emphasizing the importance of remembering those still in search of their medical breakthrough. “There are a lot of other people in the same boat as me,” she said. “We don’t have time to wait.”