New medicines have transformed cystic fibrosis for most patients, turning a debilitating lung disease into a condition that can be managed. Yet about 10% of patients have genetic mutations that prevent the treatments from working, leaving them outside one of medicine’s major advances.

“We have been left behind,” said Emily Kramer-Golinkoff, founder of Emily’s Entourage, a nonprofit created to accelerate research for what she calls “the final 10%” of patients. That group includes people who do not respond to current treatments or experience side effects.

The unmet need remains urgent after recent scientific setbacks. In May, Vertex Pharmaceuticals and Moderna stopped a clinical trial involving an mRNA treatment, citing tolerability issues, while Boehringer Ingelheim ended a cystic fibrosis gene therapy trial in February.

Kramer-Golinkoff was diagnosed with the progressive and fatal genetic disease at six weeks old, more than four decades ago. At that time, a failed clinical trial might have ended the search, but she sees continued reasons for hope through the research backed by her organization.

Cystic fibrosis affects about 40,000 Americans and causes thick, sticky mucus to accumulate in the lungs. That buildup can lead to life threatening lung infections and respiratory failure.

About 90% of patients have a genetic mutation that allows them to benefit from Trikafta and its newer version, Alyftrek, both made by Vertex. The medicines improve the function of CFTR, a protein that maintains the body’s balance of salt and water, helping thin mucus in the lungs.

Patients such as Kramer-Golinkoff do not produce a fully functional CFTR protein, so the breakthrough medicines have not brought the same results. Their disease continues to demand treatments that work through different biological approaches.

Since its creation in 2011, Emily’s Entourage has raised more than $22 million and supported 51 research projects. The funded work includes antisense oligonucleotides, also called ASOs, as well as small molecules and gene therapies.

Getting a medicine into the appropriate lung cells is a formidable scientific problem because the lung is designed to keep foreign material out. In cystic fibrosis, layers of mucus make that challenge even more severe.

“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.”

One possible option is a gene therapy developed by Spirovant Sciences that could work regardless of a patient’s particular genetic mutation. The treatment has entered an early stage clinical trial.

Emily’s Entourage is also supporting research into phages, naturally occurring viruses that kill bacteria, and antimicrobials. Those approaches target drug resistant infections that can ultimately become fatal for people with cystic fibrosis.

“We see these as buying-time initiatives,” Ghose said. The organization’s work could also help people with other conditions, including patients affected by joint and skin infections.

The nonprofit is funding research into nonsense mutations, changes in DNA that cause cells to stop making proteins earlier than they should. Findings from that work could become relevant to patients with a range of rare genetic conditions.

“We all benefit when there’s a leap forward,” Kramer-Golinkoff said. She also sees hope in the story of Baby KJ, which has prompted regulatory changes intended to let scientists develop custom made medicines for individual patients.

About 2,000 genetic mutations cause cystic fibrosis, and many are extremely rare, affecting only a small handful of people. Kramer-Golinkoff says one of the biggest obstacles is the mistaken belief that progress for most patients means the disease has been cured.

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

Now 41, Kramer-Golinkoff takes antibiotics for chronic lung infections, uses supplemental oxygen around the clock, injects multiple shots for diabetes related to cystic fibrosis and takes more than 30 pills. Those measures are intended to preserve her remaining lung function and delay the disease’s progression.

Most cystic fibrosis patients at her stage are dying or receive lung transplants, according to the source account. Kramer-Golinkoff remains grateful to be alive, but she is focused on patients still waiting for a treatment that can change their lives.

“There are a lot of other people in the same boat as me,” she said. “We don’t have time to wait.”