In the fight against cystic fibrosis (CF), one of the most common and deadly genetic diseases in the U.S., patients like Emily Kramer-Golinkoff continue to face immense challenges, particularly those with rare mutations of the disease. These mutations, which are responsible for the malfunctioning CFTR protein that leads to the accumulation of thick mucus in the lungs and other organs, prevent the lungs from staying hydrated, leading to infections, blockages, and, over time, irreversible damage. Emily, who was diagnosed with cystic fibrosis when she was just six weeks old, has dedicated her life to advocating for better treatment options, particularly for those whose CF mutations are less common and harder to treat with the current therapies available.
At 40, Emily has seen her disease progress despite her best efforts to manage it. From earning a master’s degree in bioethics to working, traveling, and spending quality time with loved ones, she has faced a difficult battle against the physical limitations of her illness. But with CF-related diabetes, chronic infections, and a life lived in isolation since the pandemic, Emily’s daily struggle is a stark reminder of the dire need for advancements in treatments, especially for those whose CF mutations don’t respond to current therapies.
While some progress has been made in the treatment of cystic fibrosis, especially for patients with the most common mutations, patients like Emily, who have a rare genetic mutation, are often left behind in the race for effective medications. Medications that work for 90% of CF patients are not effective for those with rare mutations, as these drugs are designed to target specific defects in the CFTR protein. Despite the enormous strides made in CF treatment, those with uncommon genetic variants of the disease are still left with limited options and fewer prospects for improvement.
In many ways, the situation reflects the challenges faced by patients with other genetic diseases, where advances in genetic science have revealed the subtle and complex mutations responsible for these brutal conditions. While new treatments are being developed for these diseases, individuals with rare mutations are often left with fewer options and must often rely on experimental treatments that hold out hope for a better future.
As Emily so poignantly expressed, “We feel such pure joy for our friends who have been lifted from this sinking ship. But we just feel so eager and desperate to join them. It’s really hard to be in this minority of people left behind.” This sense of frustration is shared by many individuals living with rare genetic mutations, who are eager for therapies that could change their lives but find themselves waiting as clinical trials and new therapies prioritize the more common mutations.
The market forces that shape the development of new medications also play a significant role in the disparity of treatment options for patients with rare genetic mutations. Pharmaceutical companies, understandably, prioritize medications for the most common mutations since these will benefit the largest number of patients. As Dr. Kiran Musunuru, a gene editing expert from the University of Pennsylvania, pointed out, “You need a sufficiently large number of patients in a major market in order for a company to be interested in going forward.” This phenomenon, he notes, can lead to what he calls “mutational discrimination,” where patients with rare mutations are left behind because they represent a smaller market that is less financially attractive to drug companies.
However, not all hope is lost for those suffering from rare genetic mutations. Charities like Emily’s Entourage, which Emily co-founded, are working tirelessly to overcome this barrier and help fund research for gene therapies that could potentially benefit patients, regardless of the mutation. Emily’s Entourage has been instrumental in jump-starting gene therapy research for cystic fibrosis, and while these treatments may not be available for several years, the mere fact that these therapies are now in trials provides a significant amount of hope for the CF community.
Emily’s Entourage, alongside other nonprofit organizations, has been critical in raising funds and awareness for gene therapies that could one day provide a solution for patients like Emily. The organization has helped fund the development of treatments that are mutation-agnostic, meaning they target all CF patients, regardless of their specific genetic mutation. For those like Emily, whose mutations are not currently targeted by available therapies, this type of treatment is the beacon of hope they have been waiting for.
Gene therapy for cystic fibrosis aims to address the root cause of the disease by delivering a correct version of the CFTR gene to cells. This new version of the gene would allow cells to produce normal CFTR proteins, thus preventing the mucus buildup that causes damage to the lungs and other organs. Currently, there are 14 experimental gene therapies in the pipeline for CF, most of which aim to be mutation-agnostic. These therapies, if successful, would offer a solution for a broad range of CF patients, including those with rare and less common mutations.
One of the most promising developments is a gene therapy sponsored by Spirovant Sciences, a company that was partially funded by Emily’s Entourage. The therapy, which began clinical trials at Columbia University in November, is a part of a 53-week study aimed at determining its safety and effectiveness. This gene therapy could represent a significant step forward for cystic fibrosis patients, and Emily, despite her ongoing health challenges, remains optimistic about the potential impact it could have.
Emily’s optimism about gene therapies, though tempered by the reality of her illness, has helped fuel her advocacy efforts. She continues to fight for better options for patients like herself, even as her own health deteriorates. At present, Emily lives with 30% lung function, suffers from kidney issues, and struggles with high blood pressure in her lungs. She depends on insulin for her diabetes and takes a significant number of pills every day to manage her condition. “You have to make really conscientious choices… throughout the day on how to use your limited energy. And that’s really difficult to do when you have big dreams and important work and life to live,” she said.
Despite the daily challenges, Emily remains determined to push forward. “We’re incredibly excited about the promise of gene therapies. They can’t come soon enough,” she said, emphasizing how critical it is for treatments to be developed for those with rare mutations, like herself. The continued progress in gene therapy research provides hope, and while the path forward is long, the CF community remains hopeful that these new therapies will eventually provide relief for everyone, regardless of the mutation that caused their disease.
In addition to her personal journey, Emily’s advocacy has brought attention to another important issue: the inequities in genetic testing for CF patients of diverse backgrounds. Despite significant advancements in genetic testing, people of African, Hispanic, and other non-European ancestries are often underrepresented in CF research. This lack of diversity in genetic testing means that patients from these communities are more likely to have mutations that are not well understood or studied, leaving them with fewer treatment options.
While there is still a long way to go to fully address these disparities, companies like GeneDx have made strides in offering more comprehensive genetic testing that includes diverse populations. However, more work needs to be done to ensure that all CF patients, regardless of their ancestry, have access to the same opportunities for effective treatments.
As the fight for better treatment options for CF patients continues, there is a growing sense of urgency among patients and advocates. The recent progress in gene therapies has provided new hope, but the path to widespread access is still long and uncertain. For patients like Emily Kramer-Golinkoff, the promise of gene therapy is a reminder that, despite the challenges, there is still hope for a future where no one with cystic fibrosis is left behind.
In the end, the work done by Emily’s Entourage and others is paving the way for a brighter future, where those with rare genetic mutations no longer have to wait in the shadows for life-saving treatments. The fight for better care, better therapies, and a more inclusive approach to genetic research is ongoing, and with each step forward, there is hope that one day, no one will be left behind in the pursuit of a cure for cystic fibrosis.
