Philadelphia — Advanced cystic fibrosis has left Emily Kramer-Golinkoff struggling to breathe, making everyday tasks like walking and showering a significant challenge. This debilitating genetic disease, the most common fatal one in the United States, affects around 40,000 individuals. However, Kramer-Golinkoff’s unique genetic mutation means that the treatments effective for 90% of cystic fibrosis patients do not apply to her. As a result, her hope rests on experimental gene therapies that offer the potential for relief.
Kramer-Golinkoff, 40, expresses profound joy for those benefiting from recent medical breakthroughs, yet her feelings are tinged with desperation as she watches friends benefit while she feels left behind. “It’s hard being part of this small group that hasn’t found relief,” she said.
The struggle isn’t solely a scientific one; market dynamics complicate matters. Because pharmaceutical companies prioritize treatments for the most common mutations, those with rarer conditions often face a lack of viable options. “A company needs a sufficient number of patients in a major market for it to be financially viable,” said Dr. Kiran Musunuru, a gene editing specialist at the University of Pennsylvania. He describes this situation as a form of “mutational discrimination.”
To counteract these commercial pressures, charities like Emily’s Entourage, co-founded by Kramer-Golinkoff, are working fervently to support research and development of gene therapies that could universally benefit patients, regardless of their specific mutations. While these therapies may take years to develop, the possibility of clinical trials ignites hope among patients and advocates. “Just having therapies in the works brings so much optimism,” she explained.
Diagnosed with cystic fibrosis at only six weeks old, Kramer-Golinkoff has spent her life battling the progression of the disease. As the CFTR protein malfunction leads to thick mucus accumulation in her lungs and other organs, the condition has steadily worsened over time despite her best efforts. While she achieved personal milestones, including a master’s degree and a fulfilling career, her health has deteriorated. She now contends with CF-related complications, living in isolation with her family in Greater Philadelphia during the pandemic.
In contrast, many cystic fibrosis patients have experienced transformative health improvements thanks to CFTR modulator therapies, which correct the faulty protein for those with the most common genetic mutation. However, these treatments exclude those with rare mutations or unclear disease-causing variations — a gap that persists due to insufficient genetic testing, particularly in underrepresented groups.
Despite advancements made by companies like GeneDx to broaden genetic screening, disparities remain. For instance, Black cystic fibrosis patients show a higher likelihood of having mutations that fail to respond to current therapies, highlighting inequalities that need addressing.
Researchers are actively exploring “mutation-agnostic” gene therapies that can potentially treat all varieties of cystic fibrosis. Dr. Garry Cutting from Johns Hopkins Cystic Fibrosis Center notes a significant focus on developing therapies that can aid patients regardless of their genetic background. Among the 14 experimental gene therapies currently being evaluated, several aim to provide a correct version of the CFTR gene for all affected individuals.
One promising treatment, partially backed by the Cystic Fibrosis Foundation, is being developed by Spirovant Sciences, which received initial funding from Emily’s Entourage. The first patient enrolled in a 53-week clinical trial received the therapy in November, marking a hopeful step forward in the search for lasting solutions.
Despite her declining health, which includes just 30% lung function and ongoing kidney issues, Kramer-Golinkoff remains optimistic. “We have to make careful choices every day about how to use our limited energy,” she shared. Yet she balances this with aspirations and work that matter deeply to her. “We are thrilled about the potential of gene therapies. They can’t arrive soon enough.”